WEBVTT - Ep 131 Parkinson’s Disease: Dopamine & discoveries

0:00:00.640 --> 0:00:01.920
<v Speaker 1>My name is Stacey.

0:00:02.520 --> 0:00:06.200
<v Speaker 2>I'm thirty five years old and at the age of

0:00:06.320 --> 0:00:10.920
<v Speaker 2>twenty nine, I was diagnosed with Parkinson's disease, specifically something

0:00:10.960 --> 0:00:16.000
<v Speaker 2>called young onset Parkinson's disease. I'm a doctor living in

0:00:16.079 --> 0:00:20.759
<v Speaker 2>Australia and my first symptoms were a trimmer in my

0:00:20.880 --> 0:00:24.760
<v Speaker 2>left hand, and I remember very clearly one day I

0:00:24.840 --> 0:00:28.400
<v Speaker 2>was just finishing up a case in the operating theater

0:00:28.920 --> 0:00:32.440
<v Speaker 2>and my consultant commented that my left hand was a

0:00:32.479 --> 0:00:35.320
<v Speaker 2>little bit shakier than usual and had asked if I

0:00:35.320 --> 0:00:36.920
<v Speaker 2>had extra coffee that day.

0:00:37.760 --> 0:00:41.080
<v Speaker 1>I didn't really think anything of it, and then a

0:00:41.159 --> 0:00:42.279
<v Speaker 1>couple of weeks later.

0:00:42.560 --> 0:00:48.240
<v Speaker 2>I remember getting the odd weird muscle twitch and again

0:00:48.400 --> 0:00:52.640
<v Speaker 2>not really thinking anything of it. And then one day

0:00:52.800 --> 0:00:56.520
<v Speaker 2>I just couldn't tie surgical knots with my left hand,

0:00:56.680 --> 0:00:58.760
<v Speaker 2>which was something I had spent a lot of time

0:00:59.480 --> 0:01:02.280
<v Speaker 2>trying to learn and had been able to do just

0:01:02.320 --> 0:01:04.600
<v Speaker 2>as well as my right hand. And suddenly, all of

0:01:04.600 --> 0:01:09.240
<v Speaker 2>a sudden, I became quite clumsy. And then over time

0:01:09.319 --> 0:01:12.840
<v Speaker 2>I started getting just a little bit more symptoms, a

0:01:12.840 --> 0:01:16.840
<v Speaker 2>little bit more twitching, getting cramps on and off and

0:01:16.880 --> 0:01:20.360
<v Speaker 2>all on my left hand side. And then so I

0:01:20.440 --> 0:01:23.320
<v Speaker 2>had mentioned this to my flatmate, who was also a doctor,

0:01:24.160 --> 0:01:27.720
<v Speaker 2>and he told me that I needed to go see

0:01:27.880 --> 0:01:31.760
<v Speaker 2>the GP, which is what I should have done a

0:01:31.760 --> 0:01:32.320
<v Speaker 2>while ago.

0:01:32.400 --> 0:01:34.119
<v Speaker 1>But I finally went and I.

0:01:34.080 --> 0:01:38.600
<v Speaker 2>Got referred to neuralgists and de Neeral just said it's

0:01:38.720 --> 0:01:42.320
<v Speaker 2>likely MS given the fact your female and young.

0:01:43.400 --> 0:01:45.640
<v Speaker 1>And so I was sent.

0:01:45.600 --> 0:01:47.680
<v Speaker 2>For an m R on and I had an m

0:01:47.720 --> 0:01:50.920
<v Speaker 2>OR I think a week or two later, and then

0:01:51.000 --> 0:01:53.240
<v Speaker 2>went to see the neuralist again and the MRI I

0:01:53.440 --> 0:01:58.840
<v Speaker 2>was perfectly clear. Theenerali just wasn't sure what was going on,

0:01:59.680 --> 0:02:02.160
<v Speaker 2>thought it might be an essential chremor so start me

0:02:02.440 --> 0:02:06.480
<v Speaker 2>on a bita blocker called penel and it got better

0:02:06.520 --> 0:02:09.600
<v Speaker 2>for a while. And that happened for a couple of months,

0:02:09.639 --> 0:02:13.200
<v Speaker 2>and then I noticed and people were commenting that I

0:02:13.240 --> 0:02:15.920
<v Speaker 2>started limping with my left leg a little bit, and

0:02:15.960 --> 0:02:19.800
<v Speaker 2>I noticed the one thing that was really really off

0:02:20.040 --> 0:02:23.840
<v Speaker 2>was I couldn't slide my left foot into my crocs

0:02:23.840 --> 0:02:26.959
<v Speaker 2>that I wore to go to operating theater. I couldn't

0:02:26.960 --> 0:02:30.000
<v Speaker 2>wiggle my toes like normal. And at this point I

0:02:30.160 --> 0:02:35.680
<v Speaker 2>was doing training for obgyn and then I had another

0:02:35.960 --> 0:02:40.440
<v Speaker 2>MRI again perfectly clear. Went back to the neuuralogist, and

0:02:40.680 --> 0:02:43.760
<v Speaker 2>by that point he noticed that I had a reduced

0:02:43.880 --> 0:02:48.359
<v Speaker 2>armswing in my left arm while walking, and he knew,

0:02:48.520 --> 0:02:53.280
<v Speaker 2>and I knew my medical studies that that was pretty

0:02:53.400 --> 0:02:58.080
<v Speaker 2>much a sign of Parkinson's city, something that we really

0:02:58.080 --> 0:03:01.079
<v Speaker 2>hadn't considered at the time. By this point, I've been

0:03:01.120 --> 0:03:04.519
<v Speaker 2>tested for pretty much everything under the sun. So then

0:03:04.600 --> 0:03:09.560
<v Speaker 2>I was sent to a very specific type of neuralis

0:03:09.919 --> 0:03:13.880
<v Speaker 2>motor movement disorder specialist who is still my neuralgists to

0:03:13.919 --> 0:03:19.359
<v Speaker 2>this day. And I had a scan called a dopamine

0:03:19.360 --> 0:03:23.320
<v Speaker 2>of tape PET scan and that should reduce dopamine on

0:03:23.360 --> 0:03:25.720
<v Speaker 2>my left side, and that was pretty much it.

0:03:26.600 --> 0:03:30.480
<v Speaker 1>So my neuralogist was lovely. He walked me at the

0:03:30.520 --> 0:03:34.520
<v Speaker 1>back door, knowing that I'd probably know people at the hospital,

0:03:36.520 --> 0:03:39.240
<v Speaker 1>and he told me to take two.

0:03:39.080 --> 0:03:43.200
<v Speaker 2>Weeks off, which is something that I really really struggled

0:03:43.200 --> 0:03:45.040
<v Speaker 2>with and said, no, I can't.

0:03:45.080 --> 0:03:47.040
<v Speaker 1>I can't stop working. I was supposed to start a

0:03:47.080 --> 0:03:47.720
<v Speaker 1>new job.

0:03:47.640 --> 0:03:52.680
<v Speaker 2>Soon, and by this point I had very few symptoms

0:03:52.720 --> 0:03:56.880
<v Speaker 2>and very very intimatetent symptoms, but my world just kind

0:03:56.880 --> 0:04:01.640
<v Speaker 2>of came crashing down and I went from working sixty

0:04:01.720 --> 0:04:05.600
<v Speaker 2>hours to working nothing. I ended up quitting the job

0:04:05.640 --> 0:04:09.160
<v Speaker 2>that I never started, and took a couple months off

0:04:09.320 --> 0:04:13.400
<v Speaker 2>how to basically deal with APPRA, which in Australia is

0:04:13.440 --> 0:04:16.920
<v Speaker 2>our regulatory body, and just make sure I was able

0:04:16.960 --> 0:04:20.200
<v Speaker 2>to safely work again and what I was able to

0:04:20.240 --> 0:04:24.279
<v Speaker 2>do and not do. And then I went and I

0:04:24.480 --> 0:04:28.400
<v Speaker 2>opened because I was just absolutely overwhelmed. So I went

0:04:28.440 --> 0:04:31.799
<v Speaker 2>and I worked all over Australia to job, still doing

0:04:31.839 --> 0:04:36.560
<v Speaker 2>mostly but eat OBGN, but also doing emergency and some

0:04:36.960 --> 0:04:41.080
<v Speaker 2>other kind of small town rural things all over Australia, and.

0:04:41.120 --> 0:04:43.680
<v Speaker 1>Also took the opportunity to travel.

0:04:44.240 --> 0:04:47.719
<v Speaker 2>All over the world, which was great, especially because my

0:04:47.880 --> 0:04:54.920
<v Speaker 2>last trip ended up being February twenty twenty and was

0:04:55.080 --> 0:04:59.520
<v Speaker 2>in Western Australia at the time that COVID broke, which

0:04:59.720 --> 0:05:05.080
<v Speaker 2>was Australia lockdown during COVID completely but Western Australia the

0:05:05.160 --> 0:05:09.640
<v Speaker 2>state was the absolute strictest of them all and I

0:05:09.760 --> 0:05:10.440
<v Speaker 2>was able.

0:05:10.200 --> 0:05:12.040
<v Speaker 1>To get up before the borders closed.

0:05:12.960 --> 0:05:17.880
<v Speaker 2>During the time, I started messaging my now husband, so

0:05:18.000 --> 0:05:21.640
<v Speaker 2>that worked out well. But then I found myself into

0:05:22.080 --> 0:05:27.920
<v Speaker 2>a research job working on COVID vaccine trials and actually

0:05:28.040 --> 0:05:32.080
<v Speaker 2>we're seeing patients undergoing those trials and then somehow from there,

0:05:32.240 --> 0:05:34.839
<v Speaker 2>I've found my way into friends with medicine, where I

0:05:34.839 --> 0:05:40.120
<v Speaker 2>am now and absolutely loving it. During the time I've

0:05:40.160 --> 0:05:45.040
<v Speaker 2>been on I can't even tell you how many medications.

0:05:45.720 --> 0:05:50.960
<v Speaker 2>Mostly my main medication is dopamine, which is something helps

0:05:51.000 --> 0:05:54.200
<v Speaker 2>me get through my day, or as Michael J. Fox

0:05:54.200 --> 0:05:56.520
<v Speaker 2>says he called it, being on the bus, getting on

0:05:56.560 --> 0:06:01.800
<v Speaker 2>the bus if you watched his documentary. I had one

0:06:01.839 --> 0:06:04.320
<v Speaker 2>of the most advanced.

0:06:03.800 --> 0:06:10.200
<v Speaker 1>Treatments for deep brain stimulation two years ago, and I

0:06:10.240 --> 0:06:11.839
<v Speaker 1>have two elect roads.

0:06:12.160 --> 0:06:15.839
<v Speaker 2>Implanted in my brain and a battery in my chest,

0:06:16.080 --> 0:06:20.640
<v Speaker 2>and those electrodes sent a continuous current to my brain.

0:06:21.440 --> 0:06:24.320
<v Speaker 2>And I'm able to change this and modify it with

0:06:24.440 --> 0:06:27.400
<v Speaker 2>an app on my phone, which is pretty crazy.

0:06:28.200 --> 0:06:30.760
<v Speaker 1>But the surgery itself was absolutely.

0:06:30.360 --> 0:06:32.720
<v Speaker 2>Terrifying for me. It was my first time in an

0:06:32.720 --> 0:06:35.560
<v Speaker 2>operating peter about.

0:06:35.279 --> 0:06:37.160
<v Speaker 1>Eighteen months at that point.

0:06:37.080 --> 0:06:40.440
<v Speaker 2>And it was like coming home and away but then

0:06:41.080 --> 0:06:44.920
<v Speaker 2>getting a massive metal halo and being bolted to an

0:06:44.960 --> 0:06:49.800
<v Speaker 2>operating table and then having your skull drilled into when

0:06:49.800 --> 0:06:54.560
<v Speaker 2>you were awhite when I was a white.

0:06:54.000 --> 0:06:57.159
<v Speaker 1>Which was absolutely terrifying.

0:06:57.400 --> 0:07:01.479
<v Speaker 2>But I'm incredibly glad I did. It helped my symptoms

0:07:01.640 --> 0:07:07.480
<v Speaker 2>a lot. It's helped me reduce my medication and kind

0:07:07.520 --> 0:07:10.480
<v Speaker 2>of continue to have a really normal life. I still

0:07:10.560 --> 0:07:14.920
<v Speaker 2>work pretty much full time, but normal hours instead of

0:07:14.960 --> 0:07:17.280
<v Speaker 2>the crazy sixty day eighty hour weeks that I was

0:07:17.320 --> 0:07:21.480
<v Speaker 2>doing before. And I've had to learn how to take

0:07:21.520 --> 0:07:25.200
<v Speaker 2>care of myself, which was something that was really hard

0:07:25.280 --> 0:07:28.760
<v Speaker 2>to do. And I still struggle with the guilt and

0:07:28.880 --> 0:07:31.440
<v Speaker 2>feeling that I'm not doing enough as a doctor and

0:07:31.520 --> 0:07:35.960
<v Speaker 2>not helping enough people. But it took a while to

0:07:36.000 --> 0:07:38.960
<v Speaker 2>realize I needed to help myself and nobody else was

0:07:39.040 --> 0:07:44.080
<v Speaker 2>going to do it. Dealing with the Parkinson's diagnosis was

0:07:44.120 --> 0:07:47.560
<v Speaker 2>the first time I saw a psychologist and psychiatrist, and

0:07:47.600 --> 0:07:52.400
<v Speaker 2>it's been incredibly helpful and actually looking after my mental health,

0:07:52.600 --> 0:07:55.760
<v Speaker 2>because the mental health side of Parkinson's is another thing

0:07:55.840 --> 0:08:01.640
<v Speaker 2>that kind of gets overlooked depressions or part of the

0:08:01.720 --> 0:08:06.160
<v Speaker 2>whole package that is Parkinson's. And even as my medication

0:08:06.280 --> 0:08:08.480
<v Speaker 2>wears off and I get into what we call an

0:08:08.480 --> 0:08:11.480
<v Speaker 2>off period, I can feel my anxiety kind of wrenching

0:08:11.560 --> 0:08:16.800
<v Speaker 2>up sometimes. My biggest help in coming to terms with

0:08:16.840 --> 0:08:21.680
<v Speaker 2>my diagnosis was actually listening to Michael J. Fox's biographies

0:08:21.760 --> 0:08:28.280
<v Speaker 2>on audiobook and just having somebody who is from my

0:08:28.400 --> 0:08:32.520
<v Speaker 2>same hometown diagnosed at the same age, and telling his story,

0:08:33.000 --> 0:08:37.120
<v Speaker 2>which was very similar to mine, was incredibly helpful because

0:08:37.520 --> 0:08:43.840
<v Speaker 2>having Parkinson's at this stage is incredibly lonely and it's

0:08:44.080 --> 0:08:50.320
<v Speaker 2>very very different than the normal later onside Parkinson's, we

0:08:50.400 --> 0:08:54.840
<v Speaker 2>don't get symptoms quite as severe as quickly. We tend

0:08:54.840 --> 0:09:01.600
<v Speaker 2>to progress slower, we tend not to have a dementia

0:09:01.720 --> 0:09:05.320
<v Speaker 2>side of things. And if you've seen Michael J. Fox's

0:09:05.679 --> 0:09:09.400
<v Speaker 2>most recent documentary, you can clearly see that he's still

0:09:09.480 --> 0:09:14.319
<v Speaker 2>sharp as attack and incredibly wedding, which has helped me.

0:09:14.400 --> 0:09:17.520
<v Speaker 1>A lot in my kind of mental health journey as well.

0:09:18.240 --> 0:09:21.160
<v Speaker 2>I have a great team behind me and I'm really

0:09:21.200 --> 0:09:23.439
<v Speaker 2>really grateful for that and great family.

0:09:24.800 --> 0:09:27.480
<v Speaker 1>And yeah, that's pretty much it.

0:10:13.760 --> 0:10:18.000
<v Speaker 3>Thank you so much for sharing your story with us,

0:10:18.080 --> 0:10:20.679
<v Speaker 3>like it's it's really we appreciate it so much. I

0:10:21.240 --> 0:10:25.559
<v Speaker 3>don't have the words. Yeah, thank you. Yeah.

0:10:25.640 --> 0:10:29.240
<v Speaker 4>Hi, I'm Aaron Welsh and I'm Erin Allman Updike.

0:10:29.200 --> 0:10:31.640
<v Speaker 3>And this is this podcast will kill you.

0:10:31.760 --> 0:10:35.160
<v Speaker 4>Welcome to this episode about Parkinson's disease.

0:10:35.559 --> 0:10:39.400
<v Speaker 3>Yeah, big episode on our list for a while. The

0:10:39.520 --> 0:10:44.160
<v Speaker 3>usual things that I say, but true every time. This was.

0:10:44.760 --> 0:10:49.520
<v Speaker 3>This was a hard one to do. Yeah, yeah, it was.

0:10:49.920 --> 0:10:55.040
<v Speaker 3>It was I found myself my grandpa had Parkinson's, died

0:10:55.080 --> 0:11:00.319
<v Speaker 3>of complications with Parkinson's, and I it was just when

0:11:00.360 --> 0:11:04.520
<v Speaker 3>I started to read, I immediately was like I have

0:11:04.559 --> 0:11:07.200
<v Speaker 3>to stop and take a step away from this and

0:11:07.240 --> 0:11:09.280
<v Speaker 3>then come back to it kind of like and then

0:11:09.440 --> 0:11:11.760
<v Speaker 3>and then I think by the end of it, especially

0:11:11.760 --> 0:11:13.480
<v Speaker 3>with some of the sources that I read, it became

0:11:13.640 --> 0:11:20.160
<v Speaker 3>very like therapeutic in a way. But yeah, it's a.

0:11:20.120 --> 0:11:22.760
<v Speaker 4>Lot, Yeah that makes sense. It hits very close to home.

0:11:23.160 --> 0:11:23.600
<v Speaker 3>Yeah.

0:11:23.760 --> 0:11:28.480
<v Speaker 4>Yeah, it's also a big one. It is as per

0:11:28.559 --> 0:11:32.640
<v Speaker 4>usual this season, yeah, every season.

0:11:32.960 --> 0:11:39.120
<v Speaker 5>Yeah, true, And because they're so so very much to cover,

0:11:39.240 --> 0:11:41.920
<v Speaker 5>I guess we should just sort of like get started

0:11:41.920 --> 0:11:43.320
<v Speaker 5>with things as soon as possible.

0:11:43.480 --> 0:11:44.040
<v Speaker 3>We should.

0:11:44.120 --> 0:11:46.240
<v Speaker 4>It's definitely quarantiny.

0:11:45.679 --> 0:11:48.640
<v Speaker 3>Time, it is. What are we drinking this week?

0:11:48.800 --> 0:11:51.440
<v Speaker 4>Well, nothing other than the Dopamini.

0:11:50.880 --> 0:11:58.400
<v Speaker 3>Teeny apologies for the name. I think it's pretty good.

0:11:58.520 --> 0:12:02.320
<v Speaker 3>It's pretty good. I love it it. And the Jopamini

0:12:02.440 --> 0:12:05.280
<v Speaker 3>tini is kind of exactly what it sounds like. It's

0:12:05.559 --> 0:12:09.200
<v Speaker 3>a martini, so really, you can choose your own adventure

0:12:09.360 --> 0:12:12.880
<v Speaker 3>for this martini. And any martini you ever do. We

0:12:13.120 --> 0:12:16.439
<v Speaker 3>are choosing to go with gin or a non alcoholic gin.

0:12:16.520 --> 0:12:19.760
<v Speaker 3>There are tons of options out there, and some sweet

0:12:19.840 --> 0:12:24.640
<v Speaker 3>vermouth changing it up a bit, and some Marishino lecre It's.

0:12:25.679 --> 0:12:29.839
<v Speaker 3>It's fantastic. What a great option it is. We'll post

0:12:29.840 --> 0:12:30.559
<v Speaker 3>the full.

0:12:30.320 --> 0:12:33.400
<v Speaker 4>Recipe for that quarantini as well as our non alcoholic

0:12:33.760 --> 0:12:36.319
<v Speaker 4>plus e burrita on our website, this podcast wiki you

0:12:36.360 --> 0:12:36.880
<v Speaker 4>dot com.

0:12:37.040 --> 0:12:41.160
<v Speaker 3>We certainly will. On our website you can find all

0:12:41.200 --> 0:12:46.120
<v Speaker 3>sorts of things, transcripts, bookshop dot org, and goodreads list,

0:12:47.080 --> 0:12:51.839
<v Speaker 3>merch Patreon sources for each and every one of our episodes.

0:12:52.520 --> 0:12:54.320
<v Speaker 3>It's just more things.

0:12:54.559 --> 0:12:56.800
<v Speaker 4>It's just all the things this podcast. Okay you dot

0:12:56.840 --> 0:12:57.520
<v Speaker 4>com check it out.

0:12:57.840 --> 0:13:01.920
<v Speaker 3>Yeah, I think I would have something like memorized, but

0:13:02.520 --> 0:13:03.200
<v Speaker 3>we say.

0:13:02.960 --> 0:13:06.200
<v Speaker 4>That literally every time, and it never will happen.

0:13:05.960 --> 0:13:09.560
<v Speaker 3>And it won't. At this point we know ourselves. Yeah,

0:13:09.600 --> 0:13:16.120
<v Speaker 3>that's fine. Should we get started on this topic. We should.

0:13:16.280 --> 0:13:19.679
<v Speaker 4>Let's take a break and get into the biology of Parkinson's.

0:13:54.559 --> 0:14:00.280
<v Speaker 4>One thing that is interesting about Parkinson's disease is that

0:14:00.880 --> 0:14:03.680
<v Speaker 4>it is, on the one hand, kind of a very

0:14:03.960 --> 0:14:11.880
<v Speaker 4>specific thing, and yet it is a highly variable disease.

0:14:13.000 --> 0:14:15.400
<v Speaker 4>So what that means for this episode is that it's

0:14:15.440 --> 0:14:21.080
<v Speaker 4>actually really simple and straightforward to explain on the one hand,

0:14:21.960 --> 0:14:26.960
<v Speaker 4>while also being a very classic TPWKY scenario, where as

0:14:26.960 --> 0:14:29.680
<v Speaker 4>soon as you start asking me questions, my answer is

0:14:29.680 --> 0:14:33.960
<v Speaker 4>going to be I don't know. So let me explain

0:14:34.000 --> 0:14:38.240
<v Speaker 4>a little bit of why that is. Parkinson's disease is

0:14:38.360 --> 0:14:43.240
<v Speaker 4>really a clinical syndrome. It's diagnosed based on clinical findings,

0:14:44.840 --> 0:14:47.760
<v Speaker 4>and what that means is that there isn't a point

0:14:48.160 --> 0:14:52.240
<v Speaker 4>during one's life where a single or even a group

0:14:52.320 --> 0:15:00.440
<v Speaker 4>of diagnostic tests can say this is Parkinson's disease period definitely. Instead,

0:15:00.560 --> 0:15:04.640
<v Speaker 4>it's diagnosed based on this compilation of symptoms and a

0:15:04.760 --> 0:15:09.800
<v Speaker 4>response to treatment that generally ends up with someone getting

0:15:09.840 --> 0:15:14.120
<v Speaker 4>a diagnosis of Parkinson's disease. And along those lines, there

0:15:14.160 --> 0:15:18.040
<v Speaker 4>are actually a lot of other conditions that look and

0:15:18.280 --> 0:15:22.880
<v Speaker 4>act much like Parkinson's disease, so much so that in fact,

0:15:23.120 --> 0:15:27.040
<v Speaker 4>the suite of like motor findings especially that we'll talk

0:15:27.080 --> 0:15:32.680
<v Speaker 4>about are called parkinsonism, and Parkinson's disease itself is the

0:15:32.720 --> 0:15:36.200
<v Speaker 4>primary and most common cause of parkinsonism, but there are

0:15:36.200 --> 0:15:39.240
<v Speaker 4>a lot of other conditions as well that fall under

0:15:39.320 --> 0:15:41.480
<v Speaker 4>this Parkinsonism's umbrella.

0:15:41.680 --> 0:15:46.000
<v Speaker 3>Right, like many different roads leading to one destination kind.

0:15:45.800 --> 0:15:48.880
<v Speaker 4>Of exactly exactly, and that is the nature of something

0:15:48.920 --> 0:15:52.680
<v Speaker 4>that's diagnosed based on like clinical signs and symptoms. Sure,

0:15:53.360 --> 0:15:56.400
<v Speaker 4>but we're going to focus on capital P Parkinson's disease

0:15:56.480 --> 0:15:59.640
<v Speaker 4>today and then if you ask questions, maybe we'll talk

0:15:59.680 --> 0:16:02.600
<v Speaker 4>about the other ones too, since again they do have

0:16:02.800 --> 0:16:07.520
<v Speaker 4>very overlapping symptoms and in some cases similar causes but

0:16:07.640 --> 0:16:10.720
<v Speaker 4>in different ways. So the way that I split up

0:16:10.760 --> 0:16:13.560
<v Speaker 4>this biology section is will go over first off, like

0:16:13.640 --> 0:16:16.040
<v Speaker 4>what are those symptoms, what does it look like if

0:16:16.040 --> 0:16:20.080
<v Speaker 4>someone has Parkinson's disease, Like how is this diagnosed? And

0:16:20.160 --> 0:16:23.760
<v Speaker 4>then we'll get into our brains to actually understand what's

0:16:23.920 --> 0:16:27.200
<v Speaker 4>happening that causes these symptoms, and then we can.

0:16:27.040 --> 0:16:28.280
<v Speaker 3>Talk about how we treat it.

0:16:29.080 --> 0:16:33.120
<v Speaker 4>So the symptoms that characterize Parkinson's disease can be divided

0:16:33.160 --> 0:16:39.600
<v Speaker 4>into motor symptoms and non motor symptoms. The motor symptoms

0:16:39.680 --> 0:16:43.600
<v Speaker 4>means movement symptoms, and these are kind of the hallmark

0:16:44.080 --> 0:16:48.560
<v Speaker 4>of Parkinson's disease. The first and one that has to

0:16:48.600 --> 0:16:50.880
<v Speaker 4>be present to be able to end up with a

0:16:50.920 --> 0:16:56.960
<v Speaker 4>diagnosis of Parkinson's is Brady kinesia, Brady means slow and

0:16:57.200 --> 0:17:00.680
<v Speaker 4>kind is like in kinesiology it means movement, So this

0:17:00.840 --> 0:17:05.000
<v Speaker 4>is a slowing of movement, meaning that people are not

0:17:05.240 --> 0:17:10.639
<v Speaker 4>able to make rapid movements anymore. This Brady kinesia often

0:17:10.680 --> 0:17:15.960
<v Speaker 4>goes along with rigidity, often what's called cog wheel rigidity.

0:17:16.119 --> 0:17:22.480
<v Speaker 4>So the muscles are kind of tensed, but not all

0:17:22.680 --> 0:17:25.679
<v Speaker 4>the time, if that makes sense, Like you can move

0:17:26.040 --> 0:17:29.160
<v Speaker 4>a person's arm, for example, and it will like give

0:17:29.200 --> 0:17:31.640
<v Speaker 4>a little and then be rigid again, and then give

0:17:31.680 --> 0:17:33.520
<v Speaker 4>a little and be tense again and give a little.

0:17:33.600 --> 0:17:36.200
<v Speaker 3>Does that kind of make sense? Yeah, Okay, it's like.

0:17:36.200 --> 0:17:39.520
<v Speaker 4>The way like the wheels on a cog like turning right.

0:17:39.520 --> 0:17:40.760
<v Speaker 4>That's why I got that description.

0:17:40.880 --> 0:17:41.240
<v Speaker 3>I don't know.

0:17:41.680 --> 0:17:49.840
<v Speaker 4>Yeah, So Brady kinesia, rigidity and a tremor and the tremor.

0:17:49.920 --> 0:17:52.720
<v Speaker 4>I think it's a lot of the press in Parkinson's.

0:17:53.480 --> 0:17:55.400
<v Speaker 4>I think a lot of people think of tremor when

0:17:55.400 --> 0:17:59.480
<v Speaker 4>they think of Parkinson's and the tremor associated with Parkinson's

0:17:59.520 --> 0:18:02.520
<v Speaker 4>disease is a resting tremor, which means when a person

0:18:02.600 --> 0:18:05.840
<v Speaker 4>is at rest and relaxed, the tremor is present and

0:18:05.880 --> 0:18:10.040
<v Speaker 4>it tends to get better with intentional movement, which is

0:18:10.119 --> 0:18:12.280
<v Speaker 4>kind of the opposite of what we tend to see

0:18:12.280 --> 0:18:15.520
<v Speaker 4>with something like an essential tremor, where you might have

0:18:15.720 --> 0:18:18.119
<v Speaker 4>more of a tremor if you're trying to do intentional

0:18:18.160 --> 0:18:19.200
<v Speaker 4>movement of some kind.

0:18:19.840 --> 0:18:24.959
<v Speaker 3>Yeah, okay, I won't. I'm I'm suppressing.

0:18:24.400 --> 0:18:28.440
<v Speaker 4>The why is that there's so many right, Yeah, we'll

0:18:28.480 --> 0:18:28.760
<v Speaker 4>get there.

0:18:28.800 --> 0:18:30.080
<v Speaker 3>We'll get there, We'll get there. Okay.

0:18:31.000 --> 0:18:34.320
<v Speaker 4>As these motor symptoms, those are the three big hallmarks

0:18:34.880 --> 0:18:39.760
<v Speaker 4>Brady kinesia, so slowing of the movements, rigidity, and tremor.

0:18:40.840 --> 0:18:42.240
<v Speaker 3>They don't all have to be present.

0:18:42.359 --> 0:18:45.959
<v Speaker 4>They often are all present, but Brady kinesia plus at

0:18:46.080 --> 0:18:51.440
<v Speaker 4>least one of the others is the kind of motor symptoms.

0:18:51.840 --> 0:18:56.280
<v Speaker 4>As these progress, they lead to things like trunkle instability,

0:18:56.359 --> 0:18:59.119
<v Speaker 4>so that means like your top half of your body

0:18:59.160 --> 0:19:02.399
<v Speaker 4>when you try to walk is unstable, or even if

0:19:02.400 --> 0:19:05.640
<v Speaker 4>you're just standing, you're kind of unstable and not able

0:19:05.680 --> 0:19:08.800
<v Speaker 4>to control the muscles in your trunk very well. And

0:19:08.840 --> 0:19:11.840
<v Speaker 4>then changes in the gate, which is often called a

0:19:11.920 --> 0:19:15.359
<v Speaker 4>kind of shuffling gait because it becomes difficult to pick

0:19:15.480 --> 0:19:17.879
<v Speaker 4>up the feet off the floor. And again all the

0:19:17.920 --> 0:19:23.600
<v Speaker 4>movements are very slow and these two things, especially combined

0:19:23.680 --> 0:19:26.600
<v Speaker 4>the trunkle instability and the shuffling gate, can put people

0:19:26.640 --> 0:19:29.760
<v Speaker 4>at pretty high risk of falls. So falls tend to

0:19:29.760 --> 0:19:34.200
<v Speaker 4>be a common complication in Parkinson's disease. And because this

0:19:34.240 --> 0:19:37.280
<v Speaker 4>can eventually also affect all of the muscles and not

0:19:37.520 --> 0:19:40.119
<v Speaker 4>just like our skeletal muscles that control our arms and

0:19:40.160 --> 0:19:44.080
<v Speaker 4>our legs, there can also eventually be things like dysphasia

0:19:44.240 --> 0:19:48.120
<v Speaker 4>or difficulty eating and swallowing, and difficulty talking as well,

0:19:48.240 --> 0:19:50.679
<v Speaker 4>So this can lead to an increased risk of things

0:19:50.720 --> 0:19:54.000
<v Speaker 4>like aspiration, pneumonia and things like that down the line.

0:19:55.040 --> 0:19:58.440
<v Speaker 4>So that's the motor half of Parkinson's disease. But then

0:19:58.440 --> 0:20:02.960
<v Speaker 4>there's a whole suite of non motor symptoms. And it

0:20:03.040 --> 0:20:06.360
<v Speaker 4>turns out we know now that the non motor symptoms

0:20:06.720 --> 0:20:11.240
<v Speaker 4>can and generally do tend to start quite a number

0:20:11.240 --> 0:20:15.120
<v Speaker 4>of years earlier than the motor symptoms. And yet these

0:20:15.160 --> 0:20:18.920
<v Speaker 4>motor symptoms are the kind of hallmarks of Parkinson's, and

0:20:19.000 --> 0:20:22.800
<v Speaker 4>so it's not until these motor symptoms arise that the

0:20:22.840 --> 0:20:25.480
<v Speaker 4>diagnosis is able to be made.

0:20:25.800 --> 0:20:30.040
<v Speaker 3>I read something really interesting about that in how like

0:20:30.600 --> 0:20:35.080
<v Speaker 3>diagnostic criteria are kind of undergoing a little bit of

0:20:35.680 --> 0:20:38.639
<v Speaker 3>a transformation right now, or people are trying to incorporate

0:20:38.720 --> 0:20:42.320
<v Speaker 3>more of the non motor symptoms, because often when the

0:20:42.320 --> 0:20:44.600
<v Speaker 3>motor symptoms arise, it's just like you said, it's like

0:20:44.680 --> 0:20:48.960
<v Speaker 3>in later stages, and so clinical trials might be targeting

0:20:49.000 --> 0:20:53.360
<v Speaker 3>things that aren't possible to target in those later stages,

0:20:53.400 --> 0:20:53.760
<v Speaker 3>and so.

0:20:53.720 --> 0:20:56.760
<v Speaker 4>On, Ooh, Aaron will get there in the event section.

0:20:56.920 --> 0:21:01.800
<v Speaker 4>Don't you worry? But one hundred percent yes, But so

0:21:01.960 --> 0:21:04.120
<v Speaker 4>what are some of these symptoms? Some of these are

0:21:04.119 --> 0:21:08.679
<v Speaker 4>considered kind of prodromal symptoms where they might be present

0:21:08.800 --> 0:21:11.920
<v Speaker 4>but very nonspecific at this point, so you might never

0:21:12.000 --> 0:21:16.600
<v Speaker 4>associate them with Parkinson's until hindsight, until many years later

0:21:16.720 --> 0:21:20.480
<v Speaker 4>and you realize, oh, these were actually symptoms of your Parkinson's.

0:21:21.480 --> 0:21:26.800
<v Speaker 4>So these are things like constipation, very very common REM

0:21:26.960 --> 0:21:31.639
<v Speaker 4>sleep disorders, which is honestly a entirely interesting probably worthy

0:21:31.640 --> 0:21:33.560
<v Speaker 4>of its whole own category. I feel like we've talked

0:21:33.560 --> 0:21:36.080
<v Speaker 4>about sleep and doing a lot of episodes on sleep.

0:21:37.240 --> 0:21:40.240
<v Speaker 4>But REM sleep is your dream sleep, like it's your

0:21:40.320 --> 0:21:43.000
<v Speaker 4>rapid eye. REM stands for rapid eye movement, and so

0:21:43.080 --> 0:21:44.840
<v Speaker 4>this is when you're having a lot of dreams and

0:21:44.920 --> 0:21:48.280
<v Speaker 4>normally during REM sleep, you don't really move, You're kind

0:21:48.320 --> 0:21:53.440
<v Speaker 4>of a tonic. In REM sleep disorders, people are very

0:21:53.520 --> 0:21:58.200
<v Speaker 4>active during REM sleep. So this includes doing things like talking, moving,

0:21:58.520 --> 0:22:02.679
<v Speaker 4>even going so far as acting out their dreams. And

0:22:02.760 --> 0:22:05.840
<v Speaker 4>this of course can potentially actually be quite dangerous if

0:22:05.840 --> 0:22:09.080
<v Speaker 4>people are getting up and moving and doing things during

0:22:09.359 --> 0:22:12.800
<v Speaker 4>REM sleep as a part of a REM sleep disorder. Okay, yeah,

0:22:12.920 --> 0:22:17.280
<v Speaker 4>this is not specific to Parkinson's, but very often seen

0:22:17.440 --> 0:22:21.680
<v Speaker 4>in people who eventually are diagnosed with Parkinson's. Then there's

0:22:21.720 --> 0:22:27.679
<v Speaker 4>also things like depression, anxiety, or general mood changes. Sometimes

0:22:27.720 --> 0:22:33.520
<v Speaker 4>we'll see things like hypotension or low blood pressure. Very interestingly,

0:22:33.680 --> 0:22:37.080
<v Speaker 4>a diminishing of the sense of smell, so either like

0:22:37.080 --> 0:22:39.920
<v Speaker 4>a complete loss of sense of smell or just your

0:22:39.960 --> 0:22:43.280
<v Speaker 4>sense of smelln't isn't as good anymore. It's called hyposmia.

0:22:43.880 --> 0:22:48.679
<v Speaker 4>Sometimes there'll be urinary symptoms like difficulty urinating or like

0:22:48.840 --> 0:22:53.600
<v Speaker 4>urinary retention that sort of thing, or erectile dysfunction. And then,

0:22:53.800 --> 0:22:56.960
<v Speaker 4>same as with our motor symptoms, these non motor symptoms

0:22:57.040 --> 0:23:02.440
<v Speaker 4>also progress over time and lead to things like fatigue, apathy.

0:23:03.200 --> 0:23:07.120
<v Speaker 4>Sometimes pain can become a pretty common symptom of Parkinson's,

0:23:07.200 --> 0:23:11.720
<v Speaker 4>especially in the later stages that hypotension can progress to

0:23:11.760 --> 0:23:15.640
<v Speaker 4>what's called dysautonomia, which is a very vague and general term,

0:23:15.640 --> 0:23:18.840
<v Speaker 4>but it just means that your autonomic nervous system isn't

0:23:18.920 --> 0:23:22.320
<v Speaker 4>regulating your blood pressure and your heart rate appropriately, So

0:23:22.359 --> 0:23:24.320
<v Speaker 4>you can have drops in your blood pressure when it

0:23:24.320 --> 0:23:26.400
<v Speaker 4>should be going up, you can have a high heart

0:23:26.440 --> 0:23:29.600
<v Speaker 4>rate when it should be going slow, et cetera. And

0:23:29.640 --> 0:23:34.320
<v Speaker 4>then eventually Parkinson's leads to dementia and can even lead

0:23:34.400 --> 0:23:44.320
<v Speaker 4>to psychosis. Parkinson's generally does not cause death outright, but Parkinson's,

0:23:44.400 --> 0:23:48.560
<v Speaker 4>because of all of these findings, often leads to a

0:23:48.640 --> 0:23:52.440
<v Speaker 4>significant amount of life lost in that people die much

0:23:52.480 --> 0:23:58.480
<v Speaker 4>earlier than they otherwise would because of Parkinson's. So that's

0:23:59.000 --> 0:24:03.280
<v Speaker 4>the symptoms and what Parkinson's looks like. There are a

0:24:03.320 --> 0:24:05.440
<v Speaker 4>couple of different things to talk about when it comes

0:24:05.480 --> 0:24:06.840
<v Speaker 4>to the path of physiology.

0:24:06.840 --> 0:24:07.800
<v Speaker 3>What the heck is going on?

0:24:08.240 --> 0:24:08.440
<v Speaker 1>Wait?

0:24:08.480 --> 0:24:11.600
<v Speaker 3>Can I ask a question first? Sure, So you said

0:24:11.640 --> 0:24:14.960
<v Speaker 3>that the non motor symptoms tend to show up earlier.

0:24:15.080 --> 0:24:18.360
<v Speaker 3>If I ask the question, how much earlier is the answer?

0:24:18.520 --> 0:24:19.240
<v Speaker 3>It depends?

0:24:19.400 --> 0:24:24.840
<v Speaker 4>It varies, You know me so well, it definitely is

0:24:24.880 --> 0:24:28.600
<v Speaker 4>that it depends. But it's often years, like okay, I

0:24:28.640 --> 0:24:31.000
<v Speaker 4>mean it could be on the order of several years.

0:24:31.000 --> 0:24:32.840
<v Speaker 4>It could be on the order of a decade or more.

0:24:33.119 --> 0:24:34.159
<v Speaker 3>Oh my gosh.

0:24:34.320 --> 0:24:38.639
<v Speaker 4>Yeah, And it's it's hard right now, like because this

0:24:38.800 --> 0:24:42.080
<v Speaker 4>is not something that we have a diagnostic.

0:24:41.440 --> 0:24:42.640
<v Speaker 3>Test for at all.

0:24:44.280 --> 0:24:50.000
<v Speaker 4>Constipation that's a very vague symptom, right, even depression, anxiety.

0:24:50.080 --> 0:24:53.000
<v Speaker 4>These are things that could be manifest that are entirely

0:24:53.119 --> 0:24:56.080
<v Speaker 4>unrelated to Parkinson's or they could be there as a

0:24:56.119 --> 0:24:59.359
<v Speaker 4>result of Parkinson's. Sure, and so it's a little bit

0:24:59.400 --> 0:25:01.240
<v Speaker 4>hard to tease out for some of these, some of

0:25:01.280 --> 0:25:04.640
<v Speaker 4>them I think are a little bit more strongly associated

0:25:04.720 --> 0:25:07.520
<v Speaker 4>with like Parkinson's, and only a few other things like

0:25:07.640 --> 0:25:11.560
<v Speaker 4>the rum sleep disorders for example, so that you might

0:25:11.600 --> 0:25:13.639
<v Speaker 4>be able to say, Okay, well this started, you know,

0:25:14.160 --> 0:25:17.159
<v Speaker 4>three years before your Parkinson's diagnosis or something like that.

0:25:18.160 --> 0:25:21.120
<v Speaker 4>But in any case, all of these, especially the non

0:25:21.160 --> 0:25:25.920
<v Speaker 4>motor prodromal symptoms, often start years before a Parkinson's diagnosis.

0:25:27.000 --> 0:25:29.120
<v Speaker 3>Okay. So there's two.

0:25:28.920 --> 0:25:31.240
<v Speaker 4>Things to talk about when it comes to the kind

0:25:31.240 --> 0:25:33.320
<v Speaker 4>of path of physiology of what's going on in our brain.

0:25:33.760 --> 0:25:37.159
<v Speaker 4>There's what has happened and what is happening in the

0:25:37.200 --> 0:25:41.440
<v Speaker 4>brain of someone with Parkinson's and why that finding what's

0:25:41.480 --> 0:25:44.359
<v Speaker 4>happening in the brain leads to these symptoms that we

0:25:44.480 --> 0:25:49.439
<v Speaker 4>just described. And then there's our favorite question on this podcast,

0:25:50.200 --> 0:25:53.200
<v Speaker 4>how does this happen? Or as you often ask Aaron,

0:25:53.480 --> 0:25:57.800
<v Speaker 4>why my favorite question? So first let me answer the

0:25:57.840 --> 0:26:01.880
<v Speaker 4>easy part, what is happening? And this is the part

0:26:01.920 --> 0:26:04.439
<v Speaker 4>where I said, in some ways it's kind of straightforward

0:26:04.480 --> 0:26:10.840
<v Speaker 4>to explain. Parkinson's disease results from destruction or degeneration of

0:26:10.880 --> 0:26:14.399
<v Speaker 4>a specific set of neurons, A lot of neurons really,

0:26:15.000 --> 0:26:18.240
<v Speaker 4>but predominantly neurons in a part of our brain that

0:26:18.280 --> 0:26:24.360
<v Speaker 4>are called the substantia Niagara pars compacta or SNPC. Okay,

0:26:25.320 --> 0:26:27.640
<v Speaker 4>I promise I'm not going to just name brain areas

0:26:27.680 --> 0:26:31.560
<v Speaker 4>for this whole episode. So this is an area of

0:26:31.600 --> 0:26:34.760
<v Speaker 4>the brain. It's specifically this little cluster of neurons in

0:26:34.800 --> 0:26:37.439
<v Speaker 4>our mid brain, which is part of our brain stem

0:26:37.640 --> 0:26:40.560
<v Speaker 4>at the base of our brain, that happens to have

0:26:41.400 --> 0:26:44.440
<v Speaker 4>a main function of being dopaminergic.

0:26:44.600 --> 0:26:45.240
<v Speaker 3>What does that mean.

0:26:45.320 --> 0:26:50.840
<v Speaker 4>It means these neurons are making dopamine. Dopamine, of course,

0:26:51.200 --> 0:26:54.800
<v Speaker 4>is one of our neurotransmitters. Most people have probably heard

0:26:54.840 --> 0:26:57.520
<v Speaker 4>of dopamine because it gets a lot of press. It

0:26:57.560 --> 0:26:59.760
<v Speaker 4>does a lot in our brain. It's one of our

0:27:00.240 --> 0:27:06.280
<v Speaker 4>happy hormones, right. This is a neurotransmitter that affects actions

0:27:06.400 --> 0:27:10.040
<v Speaker 4>in our brain. It happens to have a huge role

0:27:10.080 --> 0:27:18.720
<v Speaker 4>to play in motor control, cognition, learning, and reward, all

0:27:18.760 --> 0:27:21.399
<v Speaker 4>happening in our brain. It also does a lot of

0:27:21.440 --> 0:27:25.520
<v Speaker 4>other stuff in our GI tract, like modulating GI motility.

0:27:26.160 --> 0:27:29.760
<v Speaker 4>It helps with blood pressure maintenance, it's a precursor for

0:27:29.840 --> 0:27:31.600
<v Speaker 4>other hormones and the rest of our body.

0:27:31.640 --> 0:27:34.439
<v Speaker 3>It does a lot. I just I find it so

0:27:34.640 --> 0:27:38.720
<v Speaker 3>fascinating that it's involved in GI motility.

0:27:39.400 --> 0:27:42.320
<v Speaker 4>Have you heard aaron of like the gut brain axis? Oh? Yeah,

0:27:42.440 --> 0:27:45.360
<v Speaker 4>we should do a whole episode on that, because like dopamine, serotonin,

0:27:45.440 --> 0:27:47.840
<v Speaker 4>these things that are acting more in our guts than

0:27:47.840 --> 0:27:48.200
<v Speaker 4>our brains.

0:27:48.240 --> 0:27:50.280
<v Speaker 3>And I love it. Okay, I am, I'm writing this

0:27:50.400 --> 0:27:52.240
<v Speaker 3>down for sure. We're doing this.

0:27:52.320 --> 0:27:56.760
<v Speaker 4>Okay, cool, Okay, But back to Parkinson's Yes, yes, So,

0:27:57.560 --> 0:28:00.439
<v Speaker 4>these neurons in the SNPC.

0:28:01.480 --> 0:28:03.040
<v Speaker 3>Make dopamine.

0:28:03.320 --> 0:28:09.800
<v Speaker 4>They shuttle that dopamine through the nerve axons to another

0:28:09.840 --> 0:28:12.520
<v Speaker 4>part of our brain. Called the putamen, which is a

0:28:12.600 --> 0:28:13.960
<v Speaker 4>part of our basil ganglia.

0:28:14.000 --> 0:28:15.080
<v Speaker 3>It's deep in.

0:28:15.119 --> 0:28:20.240
<v Speaker 4>Our brain, and this area in our brain is very

0:28:20.320 --> 0:28:26.600
<v Speaker 4>specifically involved in motor control. It coordinates a huge amount,

0:28:26.640 --> 0:28:33.439
<v Speaker 4>if not almost all of our motor functions and also learning,

0:28:33.480 --> 0:28:37.959
<v Speaker 4>also speech articulation, language function, cognitive function. A lot of

0:28:38.000 --> 0:28:42.800
<v Speaker 4>different things have to pass through this basil ganglia via

0:28:43.040 --> 0:28:46.720
<v Speaker 4>these axons. So what we see in Parkinson's is that

0:28:46.920 --> 0:28:50.600
<v Speaker 4>this area of the brain and these axons, specifically what's

0:28:50.640 --> 0:28:58.520
<v Speaker 4>called the nigrostriadol pathway, gets degenerated. In the brains of

0:28:58.640 --> 0:29:03.000
<v Speaker 4>people who have died with Parkinson's, this part of their

0:29:03.040 --> 0:29:07.120
<v Speaker 4>brain is completely pale, which means that all of the

0:29:07.360 --> 0:29:10.760
<v Speaker 4>neuromelanin that is supposed to be there is gone. It's

0:29:10.800 --> 0:29:15.719
<v Speaker 4>just completely degenerated. So we see this degeneration. And the

0:29:15.760 --> 0:29:18.920
<v Speaker 4>second thing that we see is the deposition of what

0:29:18.960 --> 0:29:25.240
<v Speaker 4>are called Louis bodies. Louis bodies are these aggregates of proteins,

0:29:25.560 --> 0:29:29.600
<v Speaker 4>multiple misfolded proteins, but the primary one involved is called

0:29:29.680 --> 0:29:34.720
<v Speaker 4>alpha sin nucleon, and this is a protein that we

0:29:34.800 --> 0:29:36.720
<v Speaker 4>don't fully understand.

0:29:37.280 --> 0:29:37.840
<v Speaker 3>In our brain.

0:29:37.880 --> 0:29:39.320
<v Speaker 4>There's a lot of proteins in our brain that we

0:29:39.360 --> 0:29:43.680
<v Speaker 4>don't fully understand, and when it becomes misfolded in a

0:29:43.760 --> 0:29:48.200
<v Speaker 4>variety of different ways, it can accumulate in our neurons

0:29:48.280 --> 0:29:52.440
<v Speaker 4>and lead to further neuronal damage like Preon style, Like

0:29:52.520 --> 0:29:57.080
<v Speaker 4>Preon style, Yes, like Preon style. You can find Louis

0:29:57.080 --> 0:30:01.440
<v Speaker 4>bodies in people with Parkinson's, but also in people with Alzheimer's,

0:30:01.480 --> 0:30:04.080
<v Speaker 4>and of course there are other misfolded proteins that are

0:30:04.080 --> 0:30:07.880
<v Speaker 4>involved in Alzheimer's disease as well. Loui bodies are also

0:30:07.920 --> 0:30:11.400
<v Speaker 4>present in another disorder called dementia with Loui bodies that's

0:30:11.520 --> 0:30:14.800
<v Speaker 4>separate from Parkinson's but shares a lot of similarities. Rem

0:30:14.880 --> 0:30:18.680
<v Speaker 4>sleep disorder is one of them, and in Parkinson's, these

0:30:18.760 --> 0:30:22.520
<v Speaker 4>Loui bodies deposit in these areas we've already talked about,

0:30:22.600 --> 0:30:26.200
<v Speaker 4>like the substantium niagara, but also in a variety of

0:30:26.320 --> 0:30:31.800
<v Speaker 4>other brain regions as well, So now we know what

0:30:32.600 --> 0:30:36.400
<v Speaker 4>is happening. Neurons are being degenerated in the part of

0:30:36.440 --> 0:30:40.720
<v Speaker 4>our brain that controls dopamine production, So now we don't

0:30:40.720 --> 0:30:44.080
<v Speaker 4>have dopamine. If we don't have dopamine flowing, then our

0:30:44.160 --> 0:30:49.400
<v Speaker 4>nerves can't fire. If our nerves can't fire, specifically, the

0:30:49.440 --> 0:30:52.480
<v Speaker 4>nerves that are controlling our motor movements, we're going to

0:30:52.520 --> 0:30:56.360
<v Speaker 4>have problems with those motor movements. Specifically, we're not going

0:30:56.400 --> 0:31:00.600
<v Speaker 4>to be able to extend. Our muscles, going to become

0:31:00.680 --> 0:31:03.520
<v Speaker 4>fixed in certain positions. They're going to be rigid because

0:31:03.560 --> 0:31:07.440
<v Speaker 4>our brain can't tell them no fire again, no fire again,

0:31:07.560 --> 0:31:10.720
<v Speaker 4>or no relax again. Right, Because there's both positive and

0:31:10.760 --> 0:31:13.320
<v Speaker 4>negative pathways that have to happen for us to be

0:31:13.360 --> 0:31:18.960
<v Speaker 4>able to coordinate our movement smoothly. So that is why

0:31:19.000 --> 0:31:25.240
<v Speaker 4>we see most of the predominant symptoms of Parkinson's. It's

0:31:25.280 --> 0:31:28.240
<v Speaker 4>a lack of coordination of our muscle response.

0:31:28.960 --> 0:31:29.160
<v Speaker 1>Right.

0:31:30.960 --> 0:31:36.320
<v Speaker 3>But now the question is how and why and why?

0:31:38.000 --> 0:31:41.160
<v Speaker 4>And that is a question that we still don't know,

0:31:41.480 --> 0:31:45.040
<v Speaker 4>and it's a very highly debated topic and highly researched question.

0:31:45.400 --> 0:31:47.800
<v Speaker 3>Yeah, we know the what.

0:31:48.360 --> 0:31:51.120
<v Speaker 4>We know that alphas and nucleon and these lowy bodies

0:31:51.640 --> 0:31:58.480
<v Speaker 4>are very involved. We know that neurodegeneration is happening. But

0:31:59.160 --> 0:32:03.200
<v Speaker 4>exactly how how this process happens and the order in

0:32:03.240 --> 0:32:06.440
<v Speaker 4>which it happens is still very much up for debate.

0:32:07.080 --> 0:32:10.800
<v Speaker 4>It's not entirely clear. Is it that this protein alphasin

0:32:10.880 --> 0:32:14.200
<v Speaker 4>nucleon starts to become misfolded for one reason or another

0:32:14.240 --> 0:32:17.400
<v Speaker 4>and starts to deposit in our brain, and that is

0:32:17.440 --> 0:32:22.000
<v Speaker 4>what causes the death of the neurons or is it

0:32:22.440 --> 0:32:28.400
<v Speaker 4>inflammation because of either mitochondrial dysfunction and reactive oxygen species

0:32:28.560 --> 0:32:32.480
<v Speaker 4>formation or because of other toxic insults to the brain

0:32:33.000 --> 0:32:36.959
<v Speaker 4>over time that leads to the death of neurons and

0:32:37.080 --> 0:32:41.280
<v Speaker 4>further inflammation which then leads to protein misfolding and alphasin

0:32:41.400 --> 0:32:42.480
<v Speaker 4>nucleon deposition.

0:32:43.920 --> 0:32:47.280
<v Speaker 3>We don't know I mean, or is it are those

0:32:47.320 --> 0:32:50.800
<v Speaker 3>two things mutually exclusive? Where you know what I mean?

0:32:50.880 --> 0:32:54.520
<v Speaker 3>Like if the end result is the same there exactly?

0:32:54.680 --> 0:32:57.240
<v Speaker 4>And like I said, this is a disease that can

0:32:57.320 --> 0:33:02.480
<v Speaker 4>be highly variable in presentation, in time course. And there

0:33:02.480 --> 0:33:05.280
<v Speaker 4>are a lot of other disorders that are classified as

0:33:05.400 --> 0:33:09.240
<v Speaker 4>parkinsonism because they share a lot of similar features, but

0:33:09.440 --> 0:33:14.600
<v Speaker 4>not necessarily all these same hallmarks on autopsy of the brain. Right,

0:33:14.680 --> 0:33:16.680
<v Speaker 4>so there is a lot of pathways to end to

0:33:16.760 --> 0:33:21.520
<v Speaker 4>the same result. Yeah, so we don't fully know as

0:33:21.640 --> 0:33:26.320
<v Speaker 4>usual on this podcast, but we at least know a

0:33:26.360 --> 0:33:29.400
<v Speaker 4>lot of the major players that are involved.

0:33:30.240 --> 0:33:33.520
<v Speaker 3>Does that make sense? Yeah, I still want to know

0:33:33.600 --> 0:33:37.719
<v Speaker 3>why does it happen in those regions of the brain

0:33:37.800 --> 0:33:40.800
<v Speaker 3>that it happens, Why does it tend to be associated

0:33:40.840 --> 0:33:45.080
<v Speaker 3>with older age? But yet, like what happens with early

0:33:45.160 --> 0:33:49.880
<v Speaker 3>on set Parkinson's disease, what environmental Like there's been associations

0:33:49.920 --> 0:33:53.280
<v Speaker 3>with pesticides and so on, Like, what is happening? Why

0:33:53.360 --> 0:33:54.160
<v Speaker 3>is that happening?

0:33:54.800 --> 0:33:58.680
<v Speaker 4>Yeah, so there's kind of it's interesting. So Parkinson's is

0:33:58.760 --> 0:34:02.560
<v Speaker 4>an age related disease most definitely, But like you said,

0:34:02.600 --> 0:34:05.080
<v Speaker 4>it does not mean that everyone who gets it is

0:34:05.680 --> 0:34:08.760
<v Speaker 4>old at the time of diagnosis, or even middle age

0:34:08.840 --> 0:34:12.120
<v Speaker 4>at the time of diagnosis. Twenty five percent of people

0:34:12.239 --> 0:34:16.280
<v Speaker 4>are diagnosed under age sixty five. Five to ten percent

0:34:16.320 --> 0:34:18.680
<v Speaker 4>of people who are diagnosed are under age fifty.

0:34:19.440 --> 0:34:19.840
<v Speaker 3>Wow.

0:34:20.600 --> 0:34:26.720
<v Speaker 4>And the time course can really vary because, like I said,

0:34:26.840 --> 0:34:31.880
<v Speaker 4>the prodromal symptoms can start years before the diagnosis actually happens.

0:34:32.000 --> 0:34:37.120
<v Speaker 4>Right in general, aside from age, which is like considered

0:34:37.360 --> 0:34:40.440
<v Speaker 4>the main risk factor just because the majority of people

0:34:40.480 --> 0:34:45.600
<v Speaker 4>diagnosed are over age sixty five, the two big determinants

0:34:45.600 --> 0:34:50.640
<v Speaker 4>of Parkinson's disease are genetics and environmental factors, and then

0:34:50.680 --> 0:34:53.600
<v Speaker 4>their interaction. There was a time in which it was

0:34:53.680 --> 0:34:58.279
<v Speaker 4>thought to be just genetic. It is definitely not. There

0:34:58.360 --> 0:35:02.759
<v Speaker 4>are a few monogenic forms of Parkinson's disease, and much

0:35:02.840 --> 0:35:06.400
<v Speaker 4>like what we talked about in our Migraine episode, which

0:35:06.480 --> 0:35:08.160
<v Speaker 4>aaron I was like, how have we done so many

0:35:08.200 --> 0:35:09.200
<v Speaker 4>brain episodes?

0:35:09.320 --> 0:35:10.080
<v Speaker 2>We have done that.

0:35:10.160 --> 0:35:12.520
<v Speaker 3>We did epilepsy this season, didn't we We.

0:35:12.480 --> 0:35:14.640
<v Speaker 4>Did we do epilepsy this season? Our last season, I

0:35:14.680 --> 0:35:17.759
<v Speaker 4>don't remember. We've done a lot, Yeah, we have. But

0:35:19.040 --> 0:35:23.320
<v Speaker 4>like in our Migraine episode, there are these monogenic forms

0:35:23.320 --> 0:35:27.080
<v Speaker 4>of Parkinson's disease. They are not the norm They are

0:35:27.520 --> 0:35:32.560
<v Speaker 4>definitely not the most common types of Parkinson's disease, but

0:35:32.640 --> 0:35:35.800
<v Speaker 4>they's still a very important part of the research of

0:35:35.840 --> 0:35:40.120
<v Speaker 4>Parkinson's disease because not only are these forms of Parkinson's

0:35:40.160 --> 0:35:44.400
<v Speaker 4>disease potentially good targets for things like gene therapy in

0:35:44.480 --> 0:35:48.160
<v Speaker 4>terms of treatment, but it also tells us a lot

0:35:48.200 --> 0:35:52.800
<v Speaker 4>about the underpinnings the basic pathophysiology of this disease, even

0:35:52.880 --> 0:35:53.960
<v Speaker 4>for other forms.

0:35:54.320 --> 0:35:56.640
<v Speaker 3>Right. Yeah, So there's a number.

0:35:56.320 --> 0:36:00.319
<v Speaker 4>Of specific single gene mutations, a variety of different mutations

0:36:00.360 --> 0:36:03.920
<v Speaker 4>therein that have been linked to the development of Parkinson's disease.

0:36:04.280 --> 0:36:07.320
<v Speaker 4>Some of them are related to our good friend alphas

0:36:07.360 --> 0:36:11.360
<v Speaker 4>and nucleon Some of them are related to mitochondrial dysfunction,

0:36:12.360 --> 0:36:14.560
<v Speaker 4>but it's really kind of a wide variety, so there's

0:36:14.600 --> 0:36:17.920
<v Speaker 4>not still like a clear cut answer from the genetic

0:36:17.960 --> 0:36:22.200
<v Speaker 4>side of things. You asked about environmental factors, and we

0:36:22.880 --> 0:36:26.960
<v Speaker 4>really don't know when it comes to environmental factors. There's

0:36:27.000 --> 0:36:32.239
<v Speaker 4>a few that have been identified as increasing risk of Parkinson's,

0:36:32.719 --> 0:36:38.239
<v Speaker 4>like TBI or traumatic brain injury, or pesticide exposure, And

0:36:38.280 --> 0:36:40.600
<v Speaker 4>I don't know what pesticides.

0:36:39.960 --> 0:36:43.880
<v Speaker 3>Because that's just like very variable, I know, and everything

0:36:43.920 --> 0:36:46.480
<v Speaker 3>I saw was just pesticide. And I also, to be fair,

0:36:46.520 --> 0:36:49.920
<v Speaker 3>I didn't look up Parkinson's and specific pesticides, but like

0:36:50.520 --> 0:36:53.480
<v Speaker 3>it was just like pesticides. Well, because it's also.

0:36:53.280 --> 0:36:56.440
<v Speaker 4>Been linked to working in an agriculture environment, so I

0:36:56.440 --> 0:36:59.080
<v Speaker 4>think it might be like a variety of different pesticides

0:36:59.080 --> 0:37:02.560
<v Speaker 4>have been quote unquote linked to an increased risk. There

0:37:02.600 --> 0:37:05.680
<v Speaker 4>are also some exposures that seem to be related to

0:37:05.760 --> 0:37:11.400
<v Speaker 4>a decreased risk of Parkinson's, including interestingly, cigarette smoking and

0:37:11.520 --> 0:37:16.400
<v Speaker 4>coffee drinking, but there is no causal relationship that has

0:37:16.440 --> 0:37:20.720
<v Speaker 4>been linked in any of these cases. The cigarette smoking

0:37:20.760 --> 0:37:22.960
<v Speaker 4>is really interesting because some of the theories are that

0:37:23.000 --> 0:37:25.319
<v Speaker 4>it actually just has to do with how much dopamine

0:37:25.360 --> 0:37:28.799
<v Speaker 4>you have in your brain, so it just like delays

0:37:29.200 --> 0:37:32.560
<v Speaker 4>the onset of symptoms rather than actually delaying any disease

0:37:32.600 --> 0:37:37.640
<v Speaker 4>process or something like that. Huh yeah, But in any case,

0:37:37.960 --> 0:37:40.920
<v Speaker 4>we don't really know, but we know that it's not

0:37:41.160 --> 0:37:45.600
<v Speaker 4>purely genetic. So there are in fact environmental factors that

0:37:45.680 --> 0:37:47.520
<v Speaker 4>play a role in Parkinson's disease.

0:37:49.160 --> 0:37:51.160
<v Speaker 3>And then there's treatment.

0:37:52.760 --> 0:37:54.960
<v Speaker 4>And I mentioned at the top that the treatment for

0:37:55.040 --> 0:37:58.520
<v Speaker 4>Parkinson's disease is actually in some ways part of the

0:37:58.560 --> 0:38:03.040
<v Speaker 4>diagnosis of Parkinson's disease, at least at this point, because

0:38:03.080 --> 0:38:07.360
<v Speaker 4>since Parkinson's disease is at its core a disruption in

0:38:07.400 --> 0:38:11.600
<v Speaker 4>our ability to produce dopamine in our brains, like that

0:38:11.760 --> 0:38:15.200
<v Speaker 4>is what's happening in our brains. The treatment is kind

0:38:15.239 --> 0:38:19.520
<v Speaker 4>of simple. It's replacing dopamine. So we give this in

0:38:19.560 --> 0:38:22.520
<v Speaker 4>general in the form of a combination of carbon dopa

0:38:22.560 --> 0:38:25.440
<v Speaker 4>and leve doopa, which are like precursors to dopamine, so

0:38:25.480 --> 0:38:28.279
<v Speaker 4>that they last longer in our body and actually make

0:38:28.360 --> 0:38:31.360
<v Speaker 4>it into our brain rather than just staying in our bloodstream.

0:38:33.360 --> 0:38:38.520
<v Speaker 4>And if someone has these motor symptoms consistent with parkinsonism,

0:38:39.000 --> 0:38:43.520
<v Speaker 4>and they respond to dopamine like their symptoms improve usually

0:38:43.600 --> 0:38:48.080
<v Speaker 4>drastically with treatment. That's when you can be pretty sure

0:38:48.320 --> 0:38:53.560
<v Speaker 4>that the diagnosis is Parkinson's disease. Technically, still, the only

0:38:53.840 --> 0:38:58.319
<v Speaker 4>definitive diagnosis is made post mortem, with an autopsy of

0:38:58.320 --> 0:39:01.799
<v Speaker 4>the brain that shows these very spific findings associated with

0:39:01.840 --> 0:39:02.760
<v Speaker 4>Parkinson's disease.

0:39:03.800 --> 0:39:06.360
<v Speaker 3>It's really interesting to think about treatment as part of

0:39:06.360 --> 0:39:09.520
<v Speaker 3>the diagnostic criteria, like I had never that had never

0:39:09.560 --> 0:39:12.720
<v Speaker 3>occurred to me. Yeah, but it makes complete sense, like, yeah,

0:39:12.960 --> 0:39:15.480
<v Speaker 3>if you don't respond to dopamine, something else is happening,

0:39:15.719 --> 0:39:16.960
<v Speaker 3>exactly exactly.

0:39:17.520 --> 0:39:21.000
<v Speaker 4>The problem is that even in Parkinson's disease, something else

0:39:21.080 --> 0:39:25.440
<v Speaker 4>is also happening. While the substantia Niagara pars compacta and

0:39:25.480 --> 0:39:30.239
<v Speaker 4>the dopaminergic neurons therein are the primary part of our

0:39:30.280 --> 0:39:34.759
<v Speaker 4>brain that is subject to neurodegeneration in Parkinson's, it is

0:39:34.840 --> 0:39:35.960
<v Speaker 4>not the only one.

0:39:36.000 --> 0:39:36.520
<v Speaker 3>And it's not.

0:39:36.680 --> 0:39:40.799
<v Speaker 4>Only these dopamine producing neurons. We also see effect on

0:39:41.080 --> 0:39:44.720
<v Speaker 4>a lot of other neurons that produce things like acetylcholine

0:39:45.200 --> 0:39:50.120
<v Speaker 4>and norepinephrine and all of our other neurotransmitters, which is

0:39:50.239 --> 0:39:55.640
<v Speaker 4>part of why we see symptoms that aren't purely dopamine related. Right,

0:39:55.680 --> 0:39:59.080
<v Speaker 4>There's a lot of other symptoms associated with Parkinson's that

0:39:59.400 --> 0:40:05.600
<v Speaker 4>are larger than just dopamine. So treating someone with dopamine

0:40:05.800 --> 0:40:08.759
<v Speaker 4>isn't going to fix all of those symptoms, and we

0:40:08.920 --> 0:40:12.560
<v Speaker 4>don't necessarily have great treatment for all of the rest

0:40:12.600 --> 0:40:15.680
<v Speaker 4>of things aside from like treating depression if that is

0:40:15.719 --> 0:40:18.680
<v Speaker 4>a symptom, or treating low blood pressure.

0:40:18.320 --> 0:40:20.160
<v Speaker 3>If that is a symptom kind of a thing.

0:40:21.840 --> 0:40:25.040
<v Speaker 4>What we don't have at all right now are any

0:40:25.520 --> 0:40:31.480
<v Speaker 4>disease modifying therapies. So even treating someone with dopamine doesn't

0:40:31.600 --> 0:40:35.920
<v Speaker 4>change the course of disease. It improves symptoms, it improves

0:40:36.000 --> 0:40:41.160
<v Speaker 4>quality of life, but it does not change the underlying problem,

0:40:41.239 --> 0:40:43.120
<v Speaker 4>and it doesn't change the course of disease.

0:40:43.960 --> 0:40:44.200
<v Speaker 1>Right.

0:40:45.000 --> 0:40:49.960
<v Speaker 4>In addition, both Parkinson's disease itself as it progresses and

0:40:50.360 --> 0:40:56.319
<v Speaker 4>replacing that dopamine externally can actually lead to its own problems.

0:40:56.760 --> 0:41:02.360
<v Speaker 4>The side effects of this dopamine administration are called diskenesia's tardiv.

0:41:02.440 --> 0:41:05.839
<v Speaker 4>Discinesia is one of the main ones, and these are

0:41:05.880 --> 0:41:10.400
<v Speaker 4>the erratic or uncontrollable movements of the limbs or the

0:41:10.480 --> 0:41:15.160
<v Speaker 4>trunk or in tardiv diskinesia the face, things like eye blinking,

0:41:15.960 --> 0:41:20.640
<v Speaker 4>uncontrollable neck movements, or tongue movements. Some people might think

0:41:20.680 --> 0:41:25.000
<v Speaker 4>of these as hallmarks of Parkinson's disease, but really they

0:41:25.040 --> 0:41:28.880
<v Speaker 4>are an issue with the treatment for Parkinson's. It's replacing

0:41:28.920 --> 0:41:32.400
<v Speaker 4>that dopamine. So we also see these type of symptoms

0:41:32.440 --> 0:41:37.480
<v Speaker 4>in people who are on antipsychotics that are increasing the

0:41:37.520 --> 0:41:40.040
<v Speaker 4>dopamine in their brains. They can have these same kind

0:41:40.120 --> 0:41:45.760
<v Speaker 4>of symptoms. That's most of what I have for Parkinson's disease.

0:41:47.120 --> 0:41:51.920
<v Speaker 4>In terms of prognosis, It's hard to give an exact

0:41:51.960 --> 0:41:57.960
<v Speaker 4>one because despite this being very specific brain findings, it's

0:41:58.000 --> 0:42:02.400
<v Speaker 4>a very variable disease. In some of the literature, people

0:42:02.400 --> 0:42:07.040
<v Speaker 4>have started to try to classify Parkinson's into different subgroups

0:42:07.120 --> 0:42:11.040
<v Speaker 4>because of how variable the presentation can be, and there's

0:42:11.080 --> 0:42:14.520
<v Speaker 4>a few different ways that it's been done, depending on

0:42:14.560 --> 0:42:18.320
<v Speaker 4>which literature you read. One common way is to separate

0:42:18.360 --> 0:42:23.760
<v Speaker 4>it into kind of mild motor predominant, an intermediate group,

0:42:23.920 --> 0:42:27.000
<v Speaker 4>and then what's called a diffuse malignant group, or you

0:42:27.000 --> 0:42:29.680
<v Speaker 4>can think of it as very severe and very rapid

0:42:29.760 --> 0:42:34.719
<v Speaker 4>onset group. And in all of these three groups, the

0:42:34.760 --> 0:42:38.799
<v Speaker 4>prognosis is going to be very different. The duration of

0:42:38.920 --> 0:42:42.120
<v Speaker 4>disease in terms of how long you go from very

0:42:42.280 --> 0:42:46.440
<v Speaker 4>mild symptoms that are very easy to deal with to

0:42:47.200 --> 0:42:50.960
<v Speaker 4>not being able to swallow safely or not being able

0:42:51.000 --> 0:42:55.360
<v Speaker 4>to move at all. It's really highly variable. If we

0:42:55.400 --> 0:42:59.480
<v Speaker 4>think of probably the most well known individual with Parkinson's,

0:43:00.000 --> 0:43:03.839
<v Speaker 4>Michael J. Fawx, he was diagnosed at age twenty nine,

0:43:04.000 --> 0:43:07.799
<v Speaker 4>which is incredibly young. It's a very early onset form

0:43:07.800 --> 0:43:14.160
<v Speaker 4>of Parkinson's disease. He's now over sixty and still very functional.

0:43:14.600 --> 0:43:14.839
<v Speaker 3>Right.

0:43:16.160 --> 0:43:19.279
<v Speaker 4>On the other hand, there are forms of Parkinson's that

0:43:19.400 --> 0:43:24.960
<v Speaker 4>sometimes aren't ever distinguished from Parkinson's disease or one of

0:43:25.000 --> 0:43:31.040
<v Speaker 4>these other more atypical Parkinsonisms that can progress incredibly rapidly.

0:43:31.640 --> 0:43:33.840
<v Speaker 4>I had a patient that I cared for in medical

0:43:33.880 --> 0:43:37.160
<v Speaker 4>school who in the course of a few months, like

0:43:37.320 --> 0:43:40.719
<v Speaker 4>under a year, went from being someone who could kayak

0:43:40.840 --> 0:43:44.400
<v Speaker 4>and go for hikes to passing away as a result

0:43:44.640 --> 0:43:49.719
<v Speaker 4>of these Parkinson's symptoms. So there's a huge amount of variability,

0:43:50.040 --> 0:43:53.960
<v Speaker 4>which makes it really difficult not only to study, but

0:43:54.040 --> 0:43:57.279
<v Speaker 4>also to understand what is going on and how can

0:43:57.320 --> 0:43:59.560
<v Speaker 4>it be so different in different individuals.

0:43:59.800 --> 0:44:04.839
<v Speaker 3>Right like just trying to tease apart individual factors from

0:44:05.120 --> 0:44:09.160
<v Speaker 3>is it the same disease progression like everything. Yeah.

0:44:09.920 --> 0:44:10.200
<v Speaker 1>Yeah.

0:44:11.080 --> 0:44:16.200
<v Speaker 3>One thing I came across was the placebo effect and

0:44:16.239 --> 0:44:19.840
<v Speaker 3>how this seems to be kind of an interesting field

0:44:19.880 --> 0:44:24.000
<v Speaker 3>for Parkinson's disease research where a lot of the times

0:44:24.040 --> 0:44:26.719
<v Speaker 3>in like a very positive way, where there'll be a

0:44:26.760 --> 0:44:29.719
<v Speaker 3>clinical trial for a certain new type of drug or

0:44:29.719 --> 0:44:31.880
<v Speaker 3>something like that, and it turns out that both the

0:44:31.920 --> 0:44:34.960
<v Speaker 3>treatment and non treatment groups improve equally, Like there's a

0:44:34.960 --> 0:44:38.920
<v Speaker 3>strong placebo effect. And I just didn't know if you

0:44:39.160 --> 0:44:42.319
<v Speaker 3>had read anything about that or like what what that

0:44:42.400 --> 0:44:46.280
<v Speaker 3>could mean, or because like some of just the little

0:44:46.360 --> 0:44:51.720
<v Speaker 3>things about Parkinson's I find so fascinating, where in terms

0:44:51.719 --> 0:44:56.160
<v Speaker 3>of walking, sometimes people with Parkinson's can freeze, but then

0:44:56.200 --> 0:44:58.200
<v Speaker 3>if an obstacle is placed in front of them, then

0:44:58.239 --> 0:45:01.359
<v Speaker 3>they can step over it and then continue on. Like

0:45:02.080 --> 0:45:06.000
<v Speaker 3>what causes this sort of start and stop.

0:45:05.880 --> 0:45:09.440
<v Speaker 4>Start and stop? Yeah, I don't have a good answer

0:45:09.440 --> 0:45:10.839
<v Speaker 4>for that. It's really interesting.

0:45:11.680 --> 0:45:12.200
<v Speaker 3>Yeah.

0:45:12.760 --> 0:45:16.680
<v Speaker 4>I imagine it's in part because until you get very

0:45:16.800 --> 0:45:19.600
<v Speaker 4>very very late in the course of disease, it's not

0:45:19.640 --> 0:45:22.960
<v Speaker 4>like you have no dopamine whatsoever, right, and even late

0:45:23.000 --> 0:45:25.680
<v Speaker 4>in the course of disease, you have some dopamine that

0:45:25.719 --> 0:45:31.200
<v Speaker 4>still exists in the brain. So what determines how much

0:45:31.239 --> 0:45:33.640
<v Speaker 4>dopamine makes it all the way to the places that

0:45:33.680 --> 0:45:37.359
<v Speaker 4>it's supposed to bind And what other systems does our

0:45:37.360 --> 0:45:41.080
<v Speaker 4>brain have as backup to be able to keep us

0:45:41.120 --> 0:45:43.799
<v Speaker 4>functioning and moving the way that we're supposed to if

0:45:43.840 --> 0:45:46.280
<v Speaker 4>there isn't enough dopamine for those signals.

0:45:45.880 --> 0:45:48.160
<v Speaker 3>To get sent. Mm hmm, right.

0:45:49.160 --> 0:45:50.920
<v Speaker 4>I think part of what it comes back to is

0:45:50.960 --> 0:45:54.080
<v Speaker 4>that it's this is affecting the part of our brain

0:45:54.719 --> 0:46:01.480
<v Speaker 4>that is coordinating and controlling things. It's not acting directly

0:46:01.880 --> 0:46:06.520
<v Speaker 4>the motor cortex of our brain or our spinal cord

0:46:06.640 --> 0:46:12.200
<v Speaker 4>where the nerves are actually exiting and directly contracting or

0:46:12.239 --> 0:46:16.359
<v Speaker 4>relaxing muscles. Right, So the motor cortex of our brain

0:46:17.000 --> 0:46:20.759
<v Speaker 4>is what is directly sending signals to the nerves that

0:46:20.840 --> 0:46:23.480
<v Speaker 4>go to our muscles that say contract or release.

0:46:24.239 --> 0:46:27.200
<v Speaker 3>So like the messaging is messed up. All of the

0:46:27.280 --> 0:46:30.560
<v Speaker 3>systems are in place except for the control center to

0:46:30.680 --> 0:46:34.720
<v Speaker 3>carry out those actions, but like the messages stop going

0:46:34.760 --> 0:46:37.680
<v Speaker 3>out except for a few It's yes.

0:46:37.560 --> 0:46:40.160
<v Speaker 4>It's like if you think of like a nineteen fifty's

0:46:40.440 --> 0:46:43.400
<v Speaker 4>call center. You know those switchboard Yeah, yeah, people who

0:46:43.440 --> 0:46:45.319
<v Speaker 4>would be like bloop blop bloop blop boop, and like

0:46:45.400 --> 0:46:50.320
<v Speaker 4>sending messages to the right place. That part isn't working well.

0:46:50.640 --> 0:46:55.040
<v Speaker 4>But down the line, all the phone cords are still connected, right,

0:46:55.120 --> 0:46:57.359
<v Speaker 4>so some signals are going to get through and some

0:46:57.440 --> 0:46:59.320
<v Speaker 4>calls are still going to make it to the right place,

0:47:00.440 --> 0:47:06.080
<v Speaker 4>but the coordination of those messages is messed up. Okay,

0:47:07.120 --> 0:47:13.480
<v Speaker 4>that's my me, not being a brain person the way

0:47:13.480 --> 0:47:14.200
<v Speaker 4>I think about it.

0:47:14.560 --> 0:47:20.040
<v Speaker 3>Yeah, Beyond el dopa, there are other options, right, like

0:47:20.400 --> 0:47:25.440
<v Speaker 3>deep brain stimulation, exercise or like physical therapy and stuff

0:47:25.480 --> 0:47:25.680
<v Speaker 3>like that.

0:47:26.480 --> 0:47:31.600
<v Speaker 4>Absolutely, yeah, yeah, deep brain stimulation is one that I

0:47:31.640 --> 0:47:34.160
<v Speaker 4>don't know very much about, but definitely exists as an option,

0:47:34.280 --> 0:47:38.680
<v Speaker 4>especially for when el dopa stops working very well and

0:47:38.760 --> 0:47:42.759
<v Speaker 4>like later in the course of disease. And then there

0:47:42.800 --> 0:47:45.280
<v Speaker 4>are a lot of other things physical therapy not only

0:47:45.280 --> 0:47:49.920
<v Speaker 4>for just like muscles fall prevention, but also physical activity

0:47:49.920 --> 0:47:53.960
<v Speaker 4>increases our dopamine levels, So things that are increasing dopamine

0:47:53.960 --> 0:47:56.480
<v Speaker 4>are also going to be helpful. And it's interesting that

0:47:56.640 --> 0:47:58.600
<v Speaker 4>was what I thought of when you were saying that

0:47:59.080 --> 0:48:02.880
<v Speaker 4>the placebo e fact seems very strong in.

0:48:02.800 --> 0:48:04.480
<v Speaker 3>People with Parkinson's.

0:48:04.480 --> 0:48:07.520
<v Speaker 4>And I do wonder because we don't understand the Placino effect.

0:48:07.560 --> 0:48:10.200
<v Speaker 4>I mean, anyone can have a Placbo effect. Pacibo effect

0:48:10.239 --> 0:48:11.640
<v Speaker 4>is awesome. We have.

0:48:12.040 --> 0:48:12.839
<v Speaker 3>It's pretty cool.

0:48:12.960 --> 0:48:16.920
<v Speaker 4>It's fascinating and very cool, and I wonder, like how

0:48:17.000 --> 0:48:20.239
<v Speaker 4>much is it it is? It is our neurotransmitters, most

0:48:20.239 --> 0:48:23.719
<v Speaker 4>likely because our brain is controlling so much. Is it

0:48:23.760 --> 0:48:26.000
<v Speaker 4>that we think that something is working and so we

0:48:26.080 --> 0:48:28.799
<v Speaker 4>are producing more dopamine and that is part of what's

0:48:29.000 --> 0:48:32.360
<v Speaker 4>telling us that something is working and serotonin and whatever else.

0:48:33.200 --> 0:48:35.560
<v Speaker 3>Ah, yeah, I mean I don't know, but I'm I'm

0:48:35.880 --> 0:48:39.120
<v Speaker 3>right now as we speak adding it to our list

0:48:39.200 --> 0:48:43.440
<v Speaker 3>of episodes topic placebo effect. That's a good one. So

0:48:43.560 --> 0:48:49.800
<v Speaker 3>that's Parkinson's disease. You're right, it's like very fairly straightforward.

0:48:49.880 --> 0:48:52.560
<v Speaker 3>But also we don't know what the heck is going

0:48:52.560 --> 0:48:53.279
<v Speaker 3>on in our brain.

0:48:53.640 --> 0:48:56.279
<v Speaker 4>Yeah, well, like we know what's going on in our brain,

0:48:56.280 --> 0:48:57.160
<v Speaker 4>we just don't know why.

0:48:57.760 --> 0:49:03.200
<v Speaker 3>Yeah yeah, And we like why does the swinging arms

0:49:03.400 --> 0:49:07.279
<v Speaker 3>when walking? Why does that stop? Like yeah? Why? Yeah?

0:49:07.360 --> 0:49:09.880
<v Speaker 4>I mean probably just too much this is me guessing,

0:49:09.920 --> 0:49:12.560
<v Speaker 4>but like too many things to coordinate, right.

0:49:12.560 --> 0:49:14.719
<v Speaker 3>Yeah, yeah, it's fascinating.

0:49:14.960 --> 0:49:15.240
<v Speaker 1>Yeah.

0:49:16.360 --> 0:49:21.440
<v Speaker 3>Yeah, well, Aaron, can I ask you.

0:49:23.600 --> 0:49:26.319
<v Speaker 4>How did we get here? Where did Parkinson's come from?

0:49:26.640 --> 0:49:29.760
<v Speaker 4>Besides our brain or maybe our environment?

0:49:29.840 --> 0:49:34.319
<v Speaker 3>I don't know. Yeah, lots of questions there. Let's take

0:49:34.320 --> 0:50:11.000
<v Speaker 3>a break and then I'll see what I can do. Aaron,

0:50:11.040 --> 0:50:14.239
<v Speaker 3>you asked, where did this come from? You know I'm

0:50:14.239 --> 0:50:17.799
<v Speaker 3>not going to be able to answer that question unfortunately. No,

0:50:19.040 --> 0:50:21.560
<v Speaker 3>And I think at this point it's not a question

0:50:21.640 --> 0:50:27.400
<v Speaker 3>that anyone can answer, at least with any level of certainty.

0:50:27.680 --> 0:50:31.520
<v Speaker 3>Humans seem to be the only species that develops Parkinson's

0:50:31.560 --> 0:50:36.960
<v Speaker 3>disease naturally, like it can be induced in animal models. Interesting,

0:50:37.440 --> 0:50:41.440
<v Speaker 3>and maybe people have hypothesized that that's due to our

0:50:42.080 --> 0:50:46.759
<v Speaker 3>pretty good longevity. We have pretty long, long longevity, as

0:50:46.960 --> 0:50:51.359
<v Speaker 3>suggesting that Parkinson's disease is more or less mostly a

0:50:51.400 --> 0:50:54.960
<v Speaker 3>disease of aging. But what about like blue whales or

0:50:55.040 --> 0:50:59.560
<v Speaker 3>giant tortoises, other creatures that have longevity. Yeah, sea turtles

0:50:59.600 --> 0:51:02.359
<v Speaker 3>live like undreds of years man. Yeah, and as far

0:51:02.400 --> 0:51:05.000
<v Speaker 3>as I have read, they have not been observed to

0:51:05.040 --> 0:51:09.080
<v Speaker 3>develop Parkinson's, So maybe it's something to do with our

0:51:09.200 --> 0:51:14.040
<v Speaker 3>human brain. I did come across one paper that refutes

0:51:14.480 --> 0:51:19.000
<v Speaker 3>the more like widely accepted preon kind of misfolded protein

0:51:19.040 --> 0:51:22.840
<v Speaker 3>model for Parkinson's, and the authors instead suggest that it

0:51:22.920 --> 0:51:26.799
<v Speaker 3>has to do with how during early human evolution, our

0:51:26.800 --> 0:51:31.000
<v Speaker 3>brain expanded in certain ways that left other parts behind.

0:51:31.520 --> 0:51:35.200
<v Speaker 3>So like the olfactory part of our brain is smaller

0:51:35.320 --> 0:51:40.040
<v Speaker 3>relative to other primates, for instance, and those areas that

0:51:40.120 --> 0:51:43.800
<v Speaker 3>didn't expand during human brain evolution maybe are more susceptible

0:51:43.920 --> 0:51:48.600
<v Speaker 3>to like neuron loss. I don't know. I also did

0:51:48.600 --> 0:51:54.319
<v Speaker 3>come across that humans have relatively fewer dopamine neurons than

0:51:54.480 --> 0:51:58.720
<v Speaker 3>other animals as a function of size. So the example

0:51:58.719 --> 0:52:01.160
<v Speaker 3>that I came across was that a mouse has roughly

0:52:01.239 --> 0:52:05.200
<v Speaker 3>twenty thousand dopamine neurons, while an average human has around

0:52:05.280 --> 0:52:08.239
<v Speaker 3>four hundred thousand, So it's only twenty times more than

0:52:08.239 --> 0:52:12.200
<v Speaker 3>a mouse, despite humans being well more than twenty times

0:52:12.200 --> 0:52:15.920
<v Speaker 3>the size of a mouse. Okay, interesting, I don't know.

0:52:16.440 --> 0:52:18.200
<v Speaker 3>And part of the reason I don't know and no

0:52:18.280 --> 0:52:21.600
<v Speaker 3>one seems to really know is that the driver's and

0:52:21.719 --> 0:52:25.399
<v Speaker 3>precise path of physiology of Parkinson's disease have not been

0:52:25.440 --> 0:52:28.600
<v Speaker 3>fully worked out right. But don't worry, there is still

0:52:28.680 --> 0:52:31.759
<v Speaker 3>so so much more to talk about in terms of

0:52:31.760 --> 0:52:35.760
<v Speaker 3>the history of Parkinson's disease, and so for now, let's

0:52:35.800 --> 0:52:38.920
<v Speaker 3>head back to the ancient world to see whether people

0:52:39.000 --> 0:52:43.680
<v Speaker 3>recognize the disease long ago. Did they? Did they? Yes,

0:52:43.800 --> 0:52:47.480
<v Speaker 3>of course they did. Hah. There's an ancient Egyptian papyrus

0:52:47.520 --> 0:52:51.839
<v Speaker 3>that describes excessive drooling in an elderly king. There are

0:52:51.960 --> 0:52:56.400
<v Speaker 3>ancient Indian texts that describe a chronic progressive condition, including

0:52:56.440 --> 0:53:00.000
<v Speaker 3>tremor and lack of movement. There are ancient Chinese teps

0:53:00.239 --> 0:53:04.680
<v Speaker 3>that describe tremor and stiffness, and one of our frequent mentions,

0:53:04.880 --> 0:53:10.440
<v Speaker 3>the ancient Greek physician Galen wrote of resting and action tremors.

0:53:11.040 --> 0:53:14.400
<v Speaker 3>What's really fascinating is that in some of the ancient

0:53:14.480 --> 0:53:18.640
<v Speaker 3>Indian and ancient Chinese texts, treatment was recommended in the

0:53:18.640 --> 0:53:24.279
<v Speaker 3>form of various herbal concoctions, often containing seeds or extracts

0:53:24.280 --> 0:53:27.920
<v Speaker 3>from seeds. And it turns out that some of those seeds,

0:53:28.040 --> 0:53:32.919
<v Speaker 3>when analyzed, you know, in the twentieth century, contain LEVDOPA

0:53:33.360 --> 0:53:38.320
<v Speaker 3>or have anti colinergic and dopaminergic properties. Is that kind

0:53:38.320 --> 0:53:43.360
<v Speaker 3>of really? I just love that, Like it probably worked. Yeah. Yeah.

0:53:43.560 --> 0:53:46.920
<v Speaker 3>There are also a handful of possible references to Parkinson's

0:53:47.120 --> 0:53:50.840
<v Speaker 3>that pop up throughout the centuries. Leonardo da Vinci wrote

0:53:50.880 --> 0:53:54.880
<v Speaker 3>about people quote whose soul cannot control their movements in

0:53:54.920 --> 0:53:58.320
<v Speaker 3>spite of the fact that their extremities are shaking continuously

0:53:58.920 --> 0:54:03.520
<v Speaker 3>end quote. There's a possible reference to Parkinson's disease in

0:54:03.640 --> 0:54:08.200
<v Speaker 3>Shakespeare's Henry the sixth Part two. Dick the butcher asks

0:54:08.360 --> 0:54:12.080
<v Speaker 3>why dost thou quiver man, and Lord say replies, the

0:54:12.200 --> 0:54:18.360
<v Speaker 3>palsy and not fear provokes me. And philosopher Thomas Hobbes,

0:54:18.440 --> 0:54:21.040
<v Speaker 3>who lived in the seventeenth century, is thought to have

0:54:21.120 --> 0:54:25.280
<v Speaker 3>had it. Quote he had the shaking palsy in his hands,

0:54:25.560 --> 0:54:29.080
<v Speaker 3>which began in France before the year sixteen fifty, when

0:54:29.080 --> 0:54:32.680
<v Speaker 3>he was aged sixty two, and has grown upon him

0:54:32.719 --> 0:54:35.239
<v Speaker 3>by degrees ever since, so that he has not been

0:54:35.280 --> 0:54:38.480
<v Speaker 3>able to write very legibly since sixteen fifty five or

0:54:38.520 --> 0:54:43.520
<v Speaker 3>sixteen sixty six. So people have clearly recognized Parkinson's disease

0:54:43.640 --> 0:54:48.480
<v Speaker 3>for a long time, But how would it get its name, like?

0:54:48.520 --> 0:54:53.760
<v Speaker 3>Who was Parkinson? Essentially? James Parkinson was born in seventeen

0:54:53.880 --> 0:54:57.200
<v Speaker 3>fifty five in London, England, and decided to follow in

0:54:57.239 --> 0:55:01.799
<v Speaker 3>his father's footsteps, training as a surgeon and apothecary, but

0:55:01.920 --> 0:55:07.160
<v Speaker 3>also becoming in the meantime a political pamphleteer, a member

0:55:07.200 --> 0:55:12.360
<v Speaker 3>of secret societies, a pacifist, a campaigner for social welfare,

0:55:12.600 --> 0:55:19.360
<v Speaker 3>involved in like mysterious plots, a paleontologist and geologist. I'm sorry, yeah,

0:55:19.400 --> 0:55:21.640
<v Speaker 3>I don't know how he had all this time. Yeah,

0:55:21.920 --> 0:55:26.640
<v Speaker 3>to also possibly be the first to describe appendicitis maybe,

0:55:27.320 --> 0:55:32.240
<v Speaker 3>and was, of course the namesake of Parkinson's disease.

0:55:33.400 --> 0:55:37.160
<v Speaker 4>Sorry, I can't get over the paleontologist too, Like what Yeah?

0:55:37.160 --> 0:55:39.760
<v Speaker 3>I think that was one of his most famous publications

0:55:39.800 --> 0:55:42.319
<v Speaker 3>was on like paleontology slash geology.

0:55:43.000 --> 0:55:47.120
<v Speaker 4>I am envious, right, I'm one of jack of all

0:55:47.160 --> 0:55:48.360
<v Speaker 4>trades that well, I mean.

0:55:48.280 --> 0:55:52.920
<v Speaker 3>Gosh, I mean I feel like you do. Thanks appreciate that.

0:55:55.400 --> 0:55:58.560
<v Speaker 3>You just have to start publishing pamphlets. Now, there you go.

0:55:58.680 --> 0:56:01.920
<v Speaker 3>I could do a pamphlet, pamphlet, will create a secret

0:56:01.960 --> 0:56:09.759
<v Speaker 3>society and then check done anyway. In eighteen seventeen, Parkinson

0:56:09.800 --> 0:56:14.600
<v Speaker 3>published a paper titled Essay on the Shaking Palsy, in

0:56:14.640 --> 0:56:18.480
<v Speaker 3>which he described six cases a combination of patients that

0:56:18.560 --> 0:56:21.960
<v Speaker 3>he had personally examined, as well as one or two

0:56:22.000 --> 0:56:26.080
<v Speaker 3>that you just saw walking around the neighborhood. I know

0:56:26.320 --> 0:56:30.600
<v Speaker 3>it's I it's amazing to me that this is the

0:56:30.719 --> 0:56:33.479
<v Speaker 3>paper and one of it, like one of the case

0:56:33.480 --> 0:56:35.959
<v Speaker 3>descriptions is literally like I did not have a chance

0:56:36.000 --> 0:56:38.080
<v Speaker 3>to talk to this person, but this is what they

0:56:38.120 --> 0:56:44.719
<v Speaker 3>looked like from AFAR. So you know, okay, eighteen seventeen

0:56:44.880 --> 0:56:49.759
<v Speaker 3>publishing standards. Yeah, no, IRB, that's for sure. No, no.

0:56:50.880 --> 0:56:55.040
<v Speaker 3>So I'm going to read a little quote from this quote.

0:56:55.520 --> 0:56:59.240
<v Speaker 3>So slight and nearly imperceptible are the inroads of this malady,

0:56:59.440 --> 0:57:03.240
<v Speaker 3>and so extremely slow its progress that the patient cannot

0:57:03.280 --> 0:57:07.960
<v Speaker 3>recall the onset. The first symptoms perceived are a slight

0:57:08.040 --> 0:57:11.920
<v Speaker 3>sense of weakness with a proneness to trembling, most commonly

0:57:12.040 --> 0:57:15.759
<v Speaker 3>in one of the hands and arms. As the disease proceeds,

0:57:15.920 --> 0:57:18.520
<v Speaker 3>the hand fails to answer the dictates of the will.

0:57:19.720 --> 0:57:22.600
<v Speaker 3>Walking becomes a task which cannot be performed with how

0:57:22.720 --> 0:57:28.200
<v Speaker 3>considerable attention care is necessary to prevent falls, difficulties increase.

0:57:28.440 --> 0:57:31.520
<v Speaker 3>Writing can now be hardly at all accomplished, and reading

0:57:31.640 --> 0:57:35.560
<v Speaker 3>from the tremulous motion is accomplished with some difficulty. End quote.

0:57:37.000 --> 0:57:40.880
<v Speaker 3>I really just liked that phrase. The hand fails to

0:57:40.920 --> 0:57:43.280
<v Speaker 3>answer the dictates of the will. Yeah.

0:57:43.680 --> 0:57:48.560
<v Speaker 4>Yeah, I feel like that's a very good descriptor of what's.

0:57:48.360 --> 0:57:53.560
<v Speaker 3>Going on in the brain. Yeah. It uses way fewer

0:57:53.600 --> 0:57:56.200
<v Speaker 3>words than what we did trying to talk about the

0:57:56.200 --> 0:57:59.120
<v Speaker 3>control tower, and it took me like forty minutes to

0:58:00.840 --> 0:58:05.320
<v Speaker 3>like the hand can't do it. And then Parkinson's in

0:58:05.360 --> 0:58:09.280
<v Speaker 3>this essay goes on to describe changes in walking, the

0:58:09.360 --> 0:58:13.000
<v Speaker 3>tendency for constipation to be a frequent symptom, and then

0:58:13.240 --> 0:58:16.880
<v Speaker 3>the final stages of disease. Parkinson also laid out some

0:58:16.960 --> 0:58:19.720
<v Speaker 3>of the ideas that he had about what caused the disease,

0:58:19.920 --> 0:58:23.200
<v Speaker 3>which he thought originated in like the spinal cord or

0:58:23.280 --> 0:58:27.760
<v Speaker 3>brainstem you know, yeah, not far off, yeah, as well

0:58:27.800 --> 0:58:34.200
<v Speaker 3>as possible treatments, mostly relating to bloodletting, but ultimately acknowledged

0:58:34.240 --> 0:58:37.960
<v Speaker 3>that nothing had an effect and said that he hoped

0:58:38.000 --> 0:58:40.840
<v Speaker 3>that that would change one day if enough people, you know,

0:58:41.200 --> 0:58:44.920
<v Speaker 3>put their attention to this, put their focus on this disease.

0:58:46.080 --> 0:58:48.800
<v Speaker 3>And at the time that it was published, the essay

0:58:48.960 --> 0:58:52.760
<v Speaker 3>didn't really make much of a splash, and he died

0:58:52.880 --> 0:58:56.440
<v Speaker 3>in eighteen twenty four, seven years after it was published,

0:58:57.520 --> 0:59:01.880
<v Speaker 3>never knowing just how famous his name would become. Wow.

0:59:02.320 --> 0:59:05.880
<v Speaker 3>And in fact, we might today call the disease by

0:59:05.920 --> 0:59:09.800
<v Speaker 3>a completely different name if it weren't for Jean Martin Scharco.

0:59:11.240 --> 0:59:15.440
<v Speaker 3>I've definitely mentioned Charco several times on the podcast before.

0:59:15.920 --> 0:59:18.680
<v Speaker 3>Very famous dude. Yeah, and he at least makes an

0:59:18.680 --> 0:59:22.960
<v Speaker 3>appearance in our episodes on multiple sclerosis and endometriosis. I

0:59:23.000 --> 0:59:27.280
<v Speaker 3>think probably other ones as well, epilepsi. I don't know.

0:59:27.920 --> 0:59:33.120
<v Speaker 3>Charco was a famous, famous medical scientist, both in his

0:59:33.280 --> 0:59:36.840
<v Speaker 3>time as well as today, and his primary interest was

0:59:36.880 --> 0:59:41.280
<v Speaker 3>in diseases of the nerves. People came from all over

0:59:41.600 --> 0:59:43.880
<v Speaker 3>to watch him lecture at the public hospital where he

0:59:43.920 --> 0:59:47.760
<v Speaker 3>worked in Paris, and the list of diseases he recognized

0:59:47.960 --> 0:59:51.480
<v Speaker 3>or described, or that have been named after him, it's

0:59:51.520 --> 0:59:56.120
<v Speaker 3>a long list. It's a very long list. Yeah. Almost

0:59:56.200 --> 1:00:00.120
<v Speaker 3>fifty years after Parkinson's essay was published, Sharko got his

1:00:00.160 --> 1:00:03.600
<v Speaker 3>hands on a copy and immediately recognized that many of

1:00:03.640 --> 1:00:07.480
<v Speaker 3>his patients seemed to have the condition that Parkinson was describing,

1:00:08.080 --> 1:00:12.200
<v Speaker 3>and so he went about systematically characterizing the disease as

1:00:12.200 --> 1:00:15.000
<v Speaker 3>he had done with other conditions. He listed the most

1:00:15.000 --> 1:00:19.760
<v Speaker 3>common symptoms tremor, rigidity, slowness, or poverty of movement, and

1:00:19.880 --> 1:00:24.240
<v Speaker 3>postural instability, all of which Parkinson had pointed out, and

1:00:24.280 --> 1:00:28.600
<v Speaker 3>then he added two more small handwriting and facial masking.

1:00:28.920 --> 1:00:32.040
<v Speaker 3>Oh yeah, facial masking. Yeah, Aaron, could you give us

1:00:32.080 --> 1:00:35.200
<v Speaker 3>a quick definition of facial masking.

1:00:35.360 --> 1:00:38.720
<v Speaker 4>Yeah, a mask faces or facial masking means like a

1:00:38.880 --> 1:00:41.640
<v Speaker 4>face that's not really able to make expression. So it's

1:00:41.640 --> 1:00:46.200
<v Speaker 4>a very expressionless face, which is really common in Parkinson's disease,

1:00:46.280 --> 1:00:47.560
<v Speaker 4>especially later in the disease.

1:00:47.840 --> 1:00:49.600
<v Speaker 3>Okay, thank you, that's what I thought it was, but

1:00:49.640 --> 1:00:53.560
<v Speaker 3>I wasn't confident enough to give a definition. Yeah, appreciate it.

1:00:55.920 --> 1:01:00.760
<v Speaker 3>Charcot also noted that tremor wasn't a consistently present symptom

1:01:01.000 --> 1:01:04.000
<v Speaker 3>and argued that because of that, the condition shouldn't be

1:01:04.040 --> 1:01:08.640
<v Speaker 3>called shaking palsy, but rather Parkinson's disease. Wow, so he

1:01:08.720 --> 1:01:14.000
<v Speaker 3>named Parkinson's disease. Charco also described brady kinesia as a

1:01:14.040 --> 1:01:18.040
<v Speaker 3>distinct symptom. Quote in some of the various patients I

1:01:18.080 --> 1:01:21.200
<v Speaker 3>showed you, you can easily recognize how difficult it is

1:01:21.240 --> 1:01:24.800
<v Speaker 3>for them to do things, even though rigidity or tremor

1:01:24.920 --> 1:01:29.360
<v Speaker 3>is not the limiting feature. Instead, even a cursory exam

1:01:29.560 --> 1:01:33.880
<v Speaker 3>demonstrates that their problem relates more to slowness in execution

1:01:34.000 --> 1:01:39.200
<v Speaker 3>of movement rather than to real weakness end quote. Charco's

1:01:39.240 --> 1:01:43.720
<v Speaker 3>contributions to Parkinson's disease went beyond adding to its description

1:01:44.080 --> 1:01:48.000
<v Speaker 3>or raising awareness of the condition among the medical community.

1:01:48.080 --> 1:01:52.440
<v Speaker 3>He also tried out all sorts of experimental therapies, medicines

1:01:52.520 --> 1:01:59.240
<v Speaker 3>such as hiosiamine derived from Jimson weed, belladonna, cannabis, arsenic opium,

1:01:59.360 --> 1:02:04.360
<v Speaker 3>and hemlo, as well as non pharmaceutical interventions like his

1:02:04.760 --> 1:02:09.360
<v Speaker 3>quote unquote shaking chair and shaking helmet. Dear. So, he

1:02:09.440 --> 1:02:13.600
<v Speaker 3>observed that symptoms sometimes got better after long carriage rides

1:02:13.960 --> 1:02:17.800
<v Speaker 3>or horseback rides, and so he thought that shaking would help.

1:02:18.880 --> 1:02:23.880
<v Speaker 3>It didn't. He did run trials and there were some benefits,

1:02:23.920 --> 1:02:27.720
<v Speaker 3>but it was due to placebo effect. And when his

1:02:27.840 --> 1:02:31.760
<v Speaker 3>shaking chair and shaking helmet didn't work, he also tried

1:02:32.080 --> 1:02:38.400
<v Speaker 3>electrical stimulation SPA treatments, even some horrible sounding contraption that

1:02:38.480 --> 1:02:43.000
<v Speaker 3>was supposed to stretch the spinal cord. Oh, dear did nothing.

1:02:43.160 --> 1:02:48.400
<v Speaker 3>That's a torture device. Yeah, I think really nothing seemed

1:02:48.400 --> 1:02:51.120
<v Speaker 3>to have an effect, and so you know, he reasoned

1:02:51.160 --> 1:02:54.440
<v Speaker 3>maybe if the cause of the disease were to be discovered,

1:02:54.880 --> 1:02:58.800
<v Speaker 3>then more effective treatments could be developed. So to try

1:02:58.800 --> 1:03:02.560
<v Speaker 3>to identify the physical basis of Parkinson's disease, he was

1:03:02.600 --> 1:03:06.600
<v Speaker 3>going to need to do a lot of autopsies, and

1:03:06.840 --> 1:03:10.040
<v Speaker 3>fortunately the hospital where he worked had no shortage of

1:03:10.040 --> 1:03:13.760
<v Speaker 3>opportunities for that since it took in many wards of

1:03:13.800 --> 1:03:18.080
<v Speaker 3>the state. Ultimately, it wasn't Sharko himself but a couple

1:03:18.080 --> 1:03:20.960
<v Speaker 3>of his students who would end up finding a hazelnut

1:03:21.080 --> 1:03:25.160
<v Speaker 3>sized lump in the right side of the midbrain, close

1:03:25.200 --> 1:03:28.400
<v Speaker 3>to the substantia nigra, and this was in a thirty

1:03:28.400 --> 1:03:32.680
<v Speaker 3>eight year old patient with Parkinson's. Wow, so maybe the

1:03:32.720 --> 1:03:38.480
<v Speaker 3>substantia nigra was where Parkinson's originated. Seemed like a reasonable hypothesis,

1:03:39.160 --> 1:03:42.920
<v Speaker 3>but no one really did anything about it for twenty

1:03:42.960 --> 1:03:48.040
<v Speaker 3>five years or so until nineteen nineteen. That was the

1:03:48.120 --> 1:03:53.320
<v Speaker 3>year that a Russian graduate student named Konstantine Tretiakov who

1:03:53.400 --> 1:03:56.959
<v Speaker 3>was working in Paris, published his findings from fifty four

1:03:57.160 --> 1:04:01.920
<v Speaker 3>autopsied brains. All of the nine from people with Parkinson's

1:04:02.080 --> 1:04:06.600
<v Speaker 3>had extensive damage to the substantia nigra, and none of

1:04:06.640 --> 1:04:11.040
<v Speaker 3>the other brains did even more compelling was his finding

1:04:11.120 --> 1:04:15.000
<v Speaker 3>of neuronal inclusions in the brains of people with Parkinson's

1:04:15.600 --> 1:04:19.320
<v Speaker 3>and that was the same finding that Fritz Louis had

1:04:19.320 --> 1:04:26.000
<v Speaker 3>previously made aka Louis Bodies Louie buddies. Okay, And this

1:04:26.320 --> 1:04:31.160
<v Speaker 3>narrowing in on what changed physiologically or physically in Parkinson's

1:04:31.200 --> 1:04:35.960
<v Speaker 3>disease really helped researchers to focus their efforts on possible treatments,

1:04:36.400 --> 1:04:39.720
<v Speaker 3>because if they knew what was actually changing and how

1:04:39.760 --> 1:04:43.240
<v Speaker 3>those changes were associated with the signs of Parkinson's disease,

1:04:43.880 --> 1:04:46.400
<v Speaker 3>then maybe they could develop a treatment to slow the

1:04:46.480 --> 1:04:50.120
<v Speaker 3>progress or at the very least alleviate the symptoms of

1:04:50.160 --> 1:04:54.520
<v Speaker 3>the condition. And that's where we find ourselves with dopamine

1:04:54.520 --> 1:05:00.600
<v Speaker 3>and eldopa. The story begins in nineteen ten. That year,

1:05:00.800 --> 1:05:05.480
<v Speaker 3>dopamine was first synthesized by researchers Burger and Ewan, who

1:05:05.520 --> 1:05:07.520
<v Speaker 3>I think were more or less just casting a wide

1:05:07.560 --> 1:05:10.400
<v Speaker 3>net for chemicals that had an effect on the sympathetic

1:05:10.400 --> 1:05:12.960
<v Speaker 3>nervous system. Seemed like a very hot time for that

1:05:13.040 --> 1:05:16.720
<v Speaker 3>kind of research, Like I couldn't get at why they

1:05:16.720 --> 1:05:19.560
<v Speaker 3>were looking at dopamine, or how they found dopamine, or

1:05:19.600 --> 1:05:21.560
<v Speaker 3>what they were looking for when they found it. Okay,

1:05:21.680 --> 1:05:25.080
<v Speaker 3>that's as far as I could discern. But at the

1:05:25.120 --> 1:05:29.720
<v Speaker 3>time of this publication and for decades after, dopamine was

1:05:29.800 --> 1:05:33.720
<v Speaker 3>not really considered anything more than an intermediate compound in

1:05:33.760 --> 1:05:37.480
<v Speaker 3>the production of adrenaline and nor adrenaline. It was just

1:05:37.520 --> 1:05:42.640
<v Speaker 3>sort of like, nah, this is unimportant by itself, right, Yeah.

1:05:42.920 --> 1:05:48.440
<v Speaker 4>Also, no, adrenaline and adrenaline are also called epinefrinin nor

1:05:48.480 --> 1:05:51.640
<v Speaker 4>epinephrine today today, Yeah, I feel like that's important because

1:05:51.640 --> 1:05:53.240
<v Speaker 4>I said nor epineffyrin earlier, so.

1:05:53.400 --> 1:05:56.560
<v Speaker 3>I know, well, and that's what like. I may have

1:05:56.680 --> 1:05:59.000
<v Speaker 3>changed it, but I think I had them both in here.

1:05:59.240 --> 1:06:01.160
<v Speaker 3>They're both so they're both correct.

1:06:01.320 --> 1:06:01.840
<v Speaker 2>Yeah.

1:06:01.920 --> 1:06:09.280
<v Speaker 3>Yeah. A year after this paper came out, d L dopa,

1:06:09.400 --> 1:06:12.640
<v Speaker 3>so like another form of el dopa, was first synthesized

1:06:12.640 --> 1:06:17.280
<v Speaker 3>by Casimir Funk, who this is a good TPWKY trivia question.

1:06:18.200 --> 1:06:20.680
<v Speaker 3>Does his name sounds familiar to you? Yeah? It does.

1:06:21.840 --> 1:06:24.160
<v Speaker 4>Oh, I feel like it's one of our chemical episodes

1:06:24.240 --> 1:06:25.560
<v Speaker 4>and it's not tilan all, is it.

1:06:26.000 --> 1:06:28.840
<v Speaker 3>No? Well maybe, I mean I don't I don't know.

1:06:32.560 --> 1:06:34.640
<v Speaker 3>I would not have gotten this. I had to search.

1:06:35.200 --> 1:06:41.360
<v Speaker 3>He coined the word vitamin. Oh. Yeah, because they're vital. Okay,

1:06:41.720 --> 1:06:45.200
<v Speaker 3>vital I mean yeah yeah. And a couple of years

1:06:45.240 --> 1:06:50.320
<v Speaker 3>after that, another researcher, Marcus Guggenheim, isolated el dopa from

1:06:50.440 --> 1:06:55.560
<v Speaker 3>fava beans, decided to try it out why don't know,

1:06:56.160 --> 1:07:00.160
<v Speaker 3>and quickly discovered its tendency to induce vomiting, but he

1:07:00.200 --> 1:07:02.800
<v Speaker 3>didn't notice any other effect, and so he just wrote

1:07:02.840 --> 1:07:06.200
<v Speaker 3>it off as a naturally occurring molecule with no real

1:07:06.320 --> 1:07:10.840
<v Speaker 3>therapeutic promise. Oh wow, yeah, like, why would anyone want

1:07:10.880 --> 1:07:14.560
<v Speaker 3>to take this? It has this horrible side effect? And

1:07:14.600 --> 1:07:17.440
<v Speaker 3>then in nineteen thirty eight, I swear we're getting there.

1:07:17.480 --> 1:07:19.040
<v Speaker 3>It's just like a lot of steps along this stree.

1:07:19.040 --> 1:07:24.320
<v Speaker 3>I love this, Okay. Researcher Peter Holtz and colleagues discovered

1:07:24.360 --> 1:07:29.840
<v Speaker 3>the enzyme dopa decarboxylase, which converts el dopa to dopamine,

1:07:30.280 --> 1:07:33.440
<v Speaker 3>and that revealed how dopamine could be created in the

1:07:33.480 --> 1:07:37.320
<v Speaker 3>brain if you gave someone el dopa, Because well, dopamine

1:07:37.400 --> 1:07:41.200
<v Speaker 3>cannot cross the blood brain barrier on its own, el

1:07:41.280 --> 1:07:45.480
<v Speaker 3>dopa can. Yeah, And by the nineteen fifties, people were

1:07:45.480 --> 1:07:50.680
<v Speaker 3>starting to suspect that maybe dopamine was actually important as

1:07:50.840 --> 1:07:53.240
<v Speaker 3>just an individual molecule.

1:07:52.920 --> 1:07:59.000
<v Speaker 4>Wow, nineteen fifties, nineteen fifty and maybe even more than important.

1:07:58.600 --> 1:08:02.720
<v Speaker 3>It was essential huh yeah. One of the most prominent

1:08:02.800 --> 1:08:06.840
<v Speaker 3>names associated with this reframing of dopamine was a Swedish

1:08:06.840 --> 1:08:11.360
<v Speaker 3>researcher named Arvid Carlson, who in the late nineteen fifties

1:08:11.600 --> 1:08:14.880
<v Speaker 3>was leading a team researching the effects of the recently

1:08:14.920 --> 1:08:19.639
<v Speaker 3>introduced to antipsychotic drug resurpene or resurpine I'm not sure.

1:08:20.439 --> 1:08:23.920
<v Speaker 3>They gave rabbits various doses and found that at higher

1:08:23.960 --> 1:08:29.400
<v Speaker 3>doses of recurpene the rabbits became paralyzed with Parkinson's like symptoms.

1:08:30.439 --> 1:08:34.240
<v Speaker 3>Carlson suggested that maybe the drug was blocking the uptake

1:08:34.320 --> 1:08:37.439
<v Speaker 3>of an essential neurotransmitter in the brain and thought that

1:08:37.720 --> 1:08:41.160
<v Speaker 3>maybe if they injected the rabbits with el dopa, then

1:08:41.240 --> 1:08:45.800
<v Speaker 3>maybe the balance of neurotransmitters like adrenaline and ner adrenaline

1:08:45.920 --> 1:08:51.200
<v Speaker 3>or epinephrin and nora openephrin would be restored. And sure enough,

1:08:51.360 --> 1:08:55.800
<v Speaker 3>the el dopa worked almost like magic. The rabbits woke

1:08:55.920 --> 1:08:59.680
<v Speaker 3>up and were moving around in no time. But was

1:08:59.720 --> 1:09:02.479
<v Speaker 3>it because because the balance had been restored or was

1:09:02.560 --> 1:09:06.559
<v Speaker 3>something else going on? When Carlson took a closer look

1:09:06.600 --> 1:09:10.120
<v Speaker 3>at the chemical makeup in the rabbit's brains. He found

1:09:10.360 --> 1:09:14.200
<v Speaker 3>that the el dopa didn't convert into adrenaline and nor

1:09:14.240 --> 1:09:19.360
<v Speaker 3>adrenaline as he had expected, but rather this supposedly unimportant

1:09:19.400 --> 1:09:24.679
<v Speaker 3>molecule dopamine. Wow, it was like, Okay, this is kind

1:09:24.720 --> 1:09:30.839
<v Speaker 3>of revolutionary. And then then not long after, researcher Kathleen

1:09:30.920 --> 1:09:35.120
<v Speaker 3>Montague demonstrated the presence of dopamine in the brain of humans,

1:09:35.600 --> 1:09:38.800
<v Speaker 3>and that was later confirmed by Carlson's lab, and they

1:09:38.800 --> 1:09:42.200
<v Speaker 3>had developed assays to measure like the amount of dopamine

1:09:42.200 --> 1:09:44.200
<v Speaker 3>in different parts of the body and different parts of

1:09:44.200 --> 1:09:48.679
<v Speaker 3>the brain, which also was like whoa, yeah, more here

1:09:48.760 --> 1:09:51.040
<v Speaker 3>going on than we thought. And so all of this

1:09:51.200 --> 1:09:55.600
<v Speaker 3>together led Carlson to suggest that dopamine was essential for

1:09:55.960 --> 1:09:59.519
<v Speaker 3>normal brain function and the control of movement, and that

1:09:59.600 --> 1:10:04.439
<v Speaker 3>adop deficiency maybe at the root of Parkinson's disease, and

1:10:04.640 --> 1:10:05.439
<v Speaker 3>that just so.

1:10:05.439 --> 1:10:08.640
<v Speaker 4>That I understand, they are like reasoning behind it was

1:10:08.840 --> 1:10:12.280
<v Speaker 4>because of the symptoms that they saw in animals who

1:10:12.280 --> 1:10:16.040
<v Speaker 4>were dopamine deficient, or that they blocked their dopamine receptors,

1:10:16.560 --> 1:10:20.280
<v Speaker 4>but not yet necessarily because they made the connection between

1:10:21.040 --> 1:10:22.920
<v Speaker 4>the neurons in the part of the brain that they

1:10:22.920 --> 1:10:27.240
<v Speaker 4>already knew were involved right from way back when that

1:10:27.360 --> 1:10:30.240
<v Speaker 4>those also happened to be the dopo energic neurons.

1:10:30.560 --> 1:10:33.960
<v Speaker 3>Right, there was still that sort of connection. So they saw, Okay,

1:10:34.000 --> 1:10:36.639
<v Speaker 3>there is something that this drug is doing to prevent

1:10:36.840 --> 1:10:40.519
<v Speaker 3>movement that's probably related to a neurotransmitter. We don't know

1:10:40.560 --> 1:10:43.280
<v Speaker 3>that it's dopamine. Okay, So then what if we gave

1:10:43.360 --> 1:10:47.959
<v Speaker 3>this neurotransmitter precursor aka L dopa dopa to the rabbits,

1:10:48.120 --> 1:10:52.160
<v Speaker 3>Maybe that'll help fix things up. Yep, it worked way

1:10:52.160 --> 1:10:54.960
<v Speaker 3>better than anticipated, and so then they took a closer look.

1:10:55.040 --> 1:10:58.120
<v Speaker 3>They were like, hey, dopamine. Dopamine seems to be the

1:10:58.160 --> 1:11:02.000
<v Speaker 3>answer here. And so since the symptoms in the rabbits

1:11:02.000 --> 1:11:06.599
<v Speaker 3>were very similar to Parkinson's disease, dopamine Parkinson's and then

1:11:06.760 --> 1:11:09.559
<v Speaker 3>we're almost getting there. I love it. We're so close.

1:11:09.600 --> 1:11:13.559
<v Speaker 3>And it's now the nineteen sixties. You said, nineteen fifty

1:11:13.600 --> 1:11:17.240
<v Speaker 3>eight is when he presented this hypothesis at the first

1:11:17.320 --> 1:11:19.720
<v Speaker 3>International Catacholamine Symposium.

1:11:19.760 --> 1:11:23.400
<v Speaker 4>Okay, I love this. What a symposium to be at, right.

1:11:24.760 --> 1:11:31.400
<v Speaker 3>It was completely rejected His hypothesis morale, his hypothesis.

1:11:30.920 --> 1:11:34.800
<v Speaker 4>Sid dopamine was involved in Parkinson's based on these findings.

1:11:34.920 --> 1:11:39.160
<v Speaker 3>Yep, yeah, fascinating. Okay, okay, yeah. They were like more data, bro,

1:11:39.680 --> 1:11:43.000
<v Speaker 3>They were like, you need more data. Also, stop with dopamine.

1:11:43.040 --> 1:11:45.360
<v Speaker 3>Dopamine's never going to happen. It doesn't have a future.

1:11:45.600 --> 1:11:50.680
<v Speaker 3>Oh my gosh, fetch that's exactly what I was thinking of.

1:11:52.600 --> 1:11:55.640
<v Speaker 3>But Carlson would get the very last laugh when he

1:11:55.760 --> 1:11:58.720
<v Speaker 3>was awarded first of all, the Nobel Prize in Physiology

1:11:59.200 --> 1:12:02.800
<v Speaker 3>or Medicine in two thousand for his revolutionary work on dopamine,

1:12:02.840 --> 1:12:06.519
<v Speaker 3>not just in Parkinson's but in general. And there were

1:12:06.600 --> 1:12:10.720
<v Speaker 3>also many other laughs along the way, because while this

1:12:10.800 --> 1:12:13.320
<v Speaker 3>hypothesis is probably not the best way to say that,

1:12:13.439 --> 1:12:19.560
<v Speaker 3>but while this hypothesis was widely rejected, it wasn't unanimously rejected.

1:12:20.320 --> 1:12:26.200
<v Speaker 3>Two Austrian researchers I apologized for my poor pronunciation. Ole

1:12:26.439 --> 1:12:31.880
<v Speaker 3>Hornikowitz and Herbert Arainger were intrigued by this idea, and

1:12:31.960 --> 1:12:35.880
<v Speaker 3>they decided to dig a bit deeper, which involved examining

1:12:35.920 --> 1:12:39.160
<v Speaker 3>some brain samples from people who had died with Parkinson's,

1:12:39.840 --> 1:12:42.760
<v Speaker 3>and sure enough, they found that the neurons in the

1:12:42.800 --> 1:12:46.080
<v Speaker 3>region of the brain that was critical for movement, they

1:12:46.080 --> 1:12:51.360
<v Speaker 3>were depleted of dopamine. Further, the substantia nigra region was

1:12:51.439 --> 1:12:58.240
<v Speaker 3>also completely missing dopamine. So finally a dopamine centered framework

1:12:58.280 --> 1:13:02.320
<v Speaker 3>of Parkinson's disease was coming to together, which was exciting

1:13:02.360 --> 1:13:04.439
<v Speaker 3>on its own because it was like, oh, my gosh,

1:13:04.479 --> 1:13:08.840
<v Speaker 3>finally we're understanding how these pieces are fitting together. But

1:13:09.000 --> 1:13:13.320
<v Speaker 3>it was also potentially revolutionary because it promised hope for

1:13:13.439 --> 1:13:17.040
<v Speaker 3>effective treatment, right because they already did the el dopa

1:13:17.080 --> 1:13:22.639
<v Speaker 3>in the rabbits exactly and at this point treatment didn't exist, right,

1:13:22.920 --> 1:13:26.280
<v Speaker 3>and so it was like it was an uncontrollable progression

1:13:26.960 --> 1:13:29.759
<v Speaker 3>and that was the state of Parkinson's at the time.

1:13:31.840 --> 1:13:36.080
<v Speaker 3>Maybe el dopa was the long awaited answer, and it

1:13:36.280 --> 1:13:41.840
<v Speaker 3>seemed so, at least initially. In nineteen sixty one, researchers

1:13:41.880 --> 1:13:46.720
<v Speaker 3>Walter Burkmeyer and Ole Hornikowitz administered small doses of el

1:13:46.760 --> 1:13:52.439
<v Speaker 3>dopa to twenty patients with advanced Parkinson's disease. Hornikowitz later

1:13:52.520 --> 1:13:57.840
<v Speaker 3>remembered the scene quote, it was a spectacular moment to

1:13:57.880 --> 1:14:00.280
<v Speaker 3>see the patients who could not walk, could not get

1:14:00.360 --> 1:14:04.360
<v Speaker 3>up from bed, could not stand up when seated, start walking.

1:14:04.960 --> 1:14:08.960
<v Speaker 3>They all performed these activities like normal. Speech became better,

1:14:09.240 --> 1:14:14.200
<v Speaker 3>they started laughing and actually crying with joy end quote wow.

1:14:15.400 --> 1:14:20.440
<v Speaker 3>And even though Hornikowitz filmed this transformation, there were still doubters,

1:14:20.760 --> 1:14:25.120
<v Speaker 3>and rightfully so. The dosages that they had given these

1:14:25.160 --> 1:14:28.680
<v Speaker 3>patients were relatively small, and only a small proportion of

1:14:28.720 --> 1:14:31.639
<v Speaker 3>el dopa is known to cross the blood brain barrier,

1:14:32.200 --> 1:14:34.920
<v Speaker 3>and so some people suggested that it was largely due

1:14:34.960 --> 1:14:39.040
<v Speaker 3>to placebo effect, which we talked about does happen, and

1:14:39.240 --> 1:14:43.080
<v Speaker 3>a double blind study supported this doubt. In some ways,

1:14:43.760 --> 1:14:46.000
<v Speaker 3>el dopa was found to be no more effective in

1:14:46.120 --> 1:14:50.000
<v Speaker 3>relieving symptoms than saline, and it was beginning to be

1:14:50.160 --> 1:14:54.280
<v Speaker 3>recognized to cause serious side effects like high blood pressure

1:14:54.320 --> 1:14:57.920
<v Speaker 3>and nausea. But the Parkinson's field wasn't ready to give

1:14:58.000 --> 1:15:00.960
<v Speaker 3>up quite yet. Maybe it was just a matter of

1:15:01.000 --> 1:15:05.800
<v Speaker 3>finding the sweet spot for dosage. George Ktesias made a

1:15:05.880 --> 1:15:09.880
<v Speaker 3>major breakthrough when he tried scaling up the dose, so

1:15:09.960 --> 1:15:14.040
<v Speaker 3>starting out small and then gradually increasing, and this helped

1:15:14.080 --> 1:15:16.880
<v Speaker 3>to limit the adverse side effects seen early on with

1:15:16.960 --> 1:15:20.360
<v Speaker 3>the early big doses, but still allowed to build up

1:15:20.439 --> 1:15:24.639
<v Speaker 3>those doses to more effective levels. Another big step forward

1:15:24.680 --> 1:15:27.800
<v Speaker 3>was the addition of carbon doopa, which allowed more of

1:15:27.840 --> 1:15:30.479
<v Speaker 3>the el dopa to pass through the blood brain barrier.

1:15:31.560 --> 1:15:35.080
<v Speaker 3>Researcher Roger Duvoissen described what happened when he gave a

1:15:35.120 --> 1:15:40.280
<v Speaker 3>patient this combo in nineteen sixty seven. Quote the effect

1:15:40.600 --> 1:15:43.720
<v Speaker 3>was so dramatic, I couldn't believe it. Patients were so

1:15:43.880 --> 1:15:46.919
<v Speaker 3>improved that they didn't look like they had Parkinson's anymore.

1:15:47.520 --> 1:15:52.000
<v Speaker 3>End quote. The dramatic transformation that eldopa had on people

1:15:52.040 --> 1:15:55.960
<v Speaker 3>with Parkinson's disease and Parkinson's like disease. If you remember

1:15:56.000 --> 1:15:59.800
<v Speaker 3>from our encephalitis lethargica episode from way back or the

1:16:00.160 --> 1:16:03.599
<v Speaker 3>slash movie Awakenings by Oliver Sachs, which we talked about

1:16:03.640 --> 1:16:09.080
<v Speaker 3>in that episode, the difference was so stark, the improvement

1:16:09.240 --> 1:16:13.439
<v Speaker 3>was so great that this was really something that had

1:16:13.600 --> 1:16:17.120
<v Speaker 3>rarely been seen before and has rarely been seen since

1:16:17.200 --> 1:16:20.880
<v Speaker 3>in the history of medicine. Truly, Like the only other

1:16:20.920 --> 1:16:24.120
<v Speaker 3>things that came to mind to me in terms of

1:16:24.160 --> 1:16:28.680
<v Speaker 3>like near instant improvement are antibiotics and insulin. Yeah, just

1:16:28.720 --> 1:16:33.600
<v Speaker 3>like immediate holy cow reversal, What is happening like or

1:16:33.680 --> 1:16:35.840
<v Speaker 3>complete elimination of symptoms.

1:16:35.439 --> 1:16:38.640
<v Speaker 4>Like changing lives immediately immediately.

1:16:38.800 --> 1:16:42.240
<v Speaker 3>Yeah, and I'm sure there are others, but the introduction

1:16:42.439 --> 1:16:47.880
<v Speaker 3>of el dopa it was absolutely revolutionary, and of course

1:16:47.920 --> 1:16:51.400
<v Speaker 3>it wasn't Sunshine and Roses Forever, which you also may

1:16:51.439 --> 1:16:55.280
<v Speaker 3>remember from r encephalitis lethargic episode. After a month or

1:16:55.320 --> 1:16:59.080
<v Speaker 3>two of taking it, people began to experience severe side effects,

1:16:59.120 --> 1:17:03.400
<v Speaker 3>including problem like you mentioned Aaron with involuntary movement, and

1:17:03.520 --> 1:17:06.960
<v Speaker 3>as time went on, people developed a tolerance for the drug,

1:17:07.160 --> 1:17:09.679
<v Speaker 3>which meant that higher and higher doses had to be given,

1:17:10.280 --> 1:17:14.600
<v Speaker 3>leading to more and more side effects like confusion, agitation, paranoia,

1:17:14.760 --> 1:17:19.839
<v Speaker 3>and hallucinations. And occasionally the drug would just randomly stop working,

1:17:20.200 --> 1:17:22.840
<v Speaker 3>almost like a switch was flipped from on to off.

1:17:24.080 --> 1:17:28.719
<v Speaker 3>There's no denying that el dopa is an incredible drug,

1:17:29.280 --> 1:17:31.960
<v Speaker 3>but it also does come at a cost, and that's

1:17:31.960 --> 1:17:34.760
<v Speaker 3>one that must be carefully weighed by people with Parkinson's

1:17:34.800 --> 1:17:38.240
<v Speaker 3>disease and their medical providers in terms of like when

1:17:38.280 --> 1:17:42.080
<v Speaker 3>to start and so on. And the trade offs inherent

1:17:42.280 --> 1:17:45.080
<v Speaker 3>with el dopa have also led people to search for

1:17:45.160 --> 1:17:50.879
<v Speaker 3>alternative therapies, from surgeries and deep brain stimulation to neural graphs,

1:17:51.439 --> 1:17:56.200
<v Speaker 3>neuroprotective treatments like MAO inhibitors which prevent the degradation of

1:17:56.240 --> 1:18:01.000
<v Speaker 3>dopamine even phase therapy. I saw mentioned Oh interesting, I

1:18:01.040 --> 1:18:04.600
<v Speaker 3>meant to read more about that. Each of those treatments

1:18:04.600 --> 1:18:07.400
<v Speaker 3>has a story, and I know that there are probably

1:18:07.479 --> 1:18:10.080
<v Speaker 3>eight million more on the horizon that you're going to

1:18:10.120 --> 1:18:13.760
<v Speaker 3>talk about, which is amazing. Not to mention, there's the

1:18:13.840 --> 1:18:17.040
<v Speaker 3>whole part about how we learned more about the genetic

1:18:17.120 --> 1:18:21.960
<v Speaker 3>and potential environmental causes of Parkinson's. But so this doesn't

1:18:21.960 --> 1:18:26.000
<v Speaker 3>turn into a million hour episode. I'm not going to

1:18:26.160 --> 1:18:30.639
<v Speaker 3>go down those rabbit holes today. I do, however, have

1:18:30.760 --> 1:18:33.840
<v Speaker 3>one more story to tell before turning it over to you.

1:18:34.920 --> 1:18:38.040
<v Speaker 3>So I told the story just now of l DOPA

1:18:38.280 --> 1:18:42.320
<v Speaker 3>and how it revolutionized treatment, and this next story is

1:18:42.479 --> 1:18:47.320
<v Speaker 3>another revolution, but of a slightly different kind. I'm thrilled.

1:18:49.360 --> 1:18:52.360
<v Speaker 3>One of the biggest challenges for many diseases that are

1:18:52.439 --> 1:18:56.759
<v Speaker 3>specific to humans is not having an appropriate animal model.

1:18:57.040 --> 1:19:00.280
<v Speaker 3>We've talked about this a bunch on the podcast. It

1:19:00.280 --> 1:19:03.040
<v Speaker 3>makes it much more difficult to test out new treatments

1:19:03.240 --> 1:19:08.280
<v Speaker 3>or conduct experiments to understand the mechanism of disease. Until

1:19:08.320 --> 1:19:11.040
<v Speaker 3>the nineteen eighties or so, there were a couple of

1:19:11.080 --> 1:19:16.840
<v Speaker 3>Parkinson's animal models, so like using the plant extract medication resurpene,

1:19:16.960 --> 1:19:20.520
<v Speaker 3>which I mentioned earlier in the Eldapa story. But apparently

1:19:20.560 --> 1:19:25.200
<v Speaker 3>that drug blocks more neurotransmitters than just dopamines, so it

1:19:25.320 --> 1:19:29.640
<v Speaker 3>wasn't It's not perfect for that, and that lack of

1:19:30.520 --> 1:19:34.799
<v Speaker 3>really good animal models did severely limit Parkinson's disease research,

1:19:35.160 --> 1:19:39.160
<v Speaker 3>especially before genetic models of disease were developed, and so

1:19:39.280 --> 1:19:42.920
<v Speaker 3>researchers were always on the hunt for better tools, and

1:19:42.960 --> 1:19:47.360
<v Speaker 3>they stumbled upon one in an unexpected place, the San

1:19:47.479 --> 1:19:53.639
<v Speaker 3>Jose County Jail OHKAY. In July nineteen eighty two, George Correo,

1:19:53.840 --> 1:19:57.040
<v Speaker 3>who was in the San Jose County Jail on drug charges,

1:19:57.520 --> 1:20:01.200
<v Speaker 3>woke up one morning unable to talk or move, but

1:20:01.280 --> 1:20:05.200
<v Speaker 3>with his senses fully intact. He was admitted to the

1:20:05.200 --> 1:20:09.080
<v Speaker 3>emergency room after his condition got worse and the doctors

1:20:09.320 --> 1:20:13.640
<v Speaker 3>could not find out what was wrong. Reflex hammer no response,

1:20:14.280 --> 1:20:19.400
<v Speaker 3>blunt pressure to fingernails, no response, ammonium sulfate smelling salts

1:20:19.840 --> 1:20:24.280
<v Speaker 3>no response. Eventually he was transferred to the psychiatric ward

1:20:24.400 --> 1:20:29.280
<v Speaker 3>and diagnosed with catatonic schizophrenia. This was a diagnosis that

1:20:29.400 --> 1:20:33.559
<v Speaker 3>stirred up some controversy among the hospital's doctors, with the

1:20:33.600 --> 1:20:37.479
<v Speaker 3>neurologists arguing that it was a psychiatric disorder and the

1:20:37.479 --> 1:20:42.040
<v Speaker 3>psychiatrists insisting insisting that it was neurologic. I have been

1:20:42.080 --> 1:20:44.000
<v Speaker 3>in the middle of one of these debates. That's cool.

1:20:46.439 --> 1:20:49.679
<v Speaker 3>And then it was the head of neurology, Bill Langston,

1:20:49.760 --> 1:20:52.879
<v Speaker 3>that got involved and decided to run a few more tests,

1:20:53.560 --> 1:20:57.000
<v Speaker 3>the results of which convinced him that they were actually

1:20:57.080 --> 1:21:01.040
<v Speaker 3>dealing with a mysterious neurological problem, so he had George

1:21:01.040 --> 1:21:04.880
<v Speaker 3>transferred to the neurobehavior unit. After a few days there,

1:21:05.160 --> 1:21:09.000
<v Speaker 3>a doctor noticed the slightest of movements from George's fingers,

1:21:09.600 --> 1:21:11.760
<v Speaker 3>and so he placed a pencil in his hands with

1:21:11.840 --> 1:21:16.519
<v Speaker 3>a notepad underneath. After about thirty minutes, George had written

1:21:16.520 --> 1:21:20.680
<v Speaker 3>his name along with quote, I'm not sure what is

1:21:20.720 --> 1:21:24.040
<v Speaker 3>happening to me. I only know I can't function normally.

1:21:24.520 --> 1:21:27.160
<v Speaker 3>I can't move right. I know what I want to do,

1:21:27.439 --> 1:21:31.280
<v Speaker 3>it just won't come out right. And he wrote all

1:21:31.320 --> 1:21:35.240
<v Speaker 3>of that. It took it took a while, but yeah, wow, yeah.

1:21:35.960 --> 1:21:39.400
<v Speaker 3>And so with this path of communication open, the doctors

1:21:39.400 --> 1:21:42.400
<v Speaker 3>began taking a detailed, or as detailed as they could,

1:21:42.520 --> 1:21:45.880
<v Speaker 3>medical history, which is how they learned that George had

1:21:45.880 --> 1:21:48.880
<v Speaker 3>taken heroin, and that he had been with his girlfriend

1:21:49.000 --> 1:21:52.640
<v Speaker 3>Juaniita Lopez before he had gotten sick. And when they

1:21:52.720 --> 1:21:55.240
<v Speaker 3>found her, because they were like okay, you know, they

1:21:55.240 --> 1:21:57.120
<v Speaker 3>were going to find out first of all if she

1:21:57.280 --> 1:22:00.439
<v Speaker 3>was okay, but also what she knew, they found that

1:22:00.479 --> 1:22:02.719
<v Speaker 3>she was in pretty much the same state that George

1:22:02.760 --> 1:22:07.160
<v Speaker 3>was in, motionless and rigid m hm. So then they

1:22:07.240 --> 1:22:10.120
<v Speaker 3>cast a wider net around the town around the area

1:22:10.560 --> 1:22:14.799
<v Speaker 3>and found more cases of people who were mysteriously frozen,

1:22:15.320 --> 1:22:19.840
<v Speaker 3>six in total, including George and Juanita, and one of

1:22:19.880 --> 1:22:26.960
<v Speaker 3>whom was a young woman who was diagnosed with hysterical paralysis. Wow. Yeah,

1:22:27.040 --> 1:22:29.599
<v Speaker 3>The link between all of them was that they had

1:22:29.720 --> 1:22:34.280
<v Speaker 3>all taken heroin or what they thought was heroin. Okay,

1:22:35.120 --> 1:22:37.920
<v Speaker 3>Testing of the substance that they had found in the

1:22:37.920 --> 1:22:41.280
<v Speaker 3>apartment of one of these patients revealed that it wasn't

1:22:41.720 --> 1:22:46.880
<v Speaker 3>actually heroin, but a designer drug synthesized in an underground

1:22:46.960 --> 1:22:52.240
<v Speaker 3>lab and sold as heroin, And somehow this substance had

1:22:52.320 --> 1:22:56.000
<v Speaker 3>induced the symptoms of Parkinson's disease in these young people

1:22:56.080 --> 1:23:00.320
<v Speaker 3>in a matter of hours. What and because it looked

1:23:00.360 --> 1:23:04.680
<v Speaker 3>like Parkinson's, why not try al dopa. When they were

1:23:04.680 --> 1:23:11.320
<v Speaker 3>given al dopa, they improved almost like almost immediately, gaining

1:23:11.439 --> 1:23:15.080
<v Speaker 3>full control over their bodies, at least until the side

1:23:15.080 --> 1:23:21.040
<v Speaker 3>effects started. But this improvement, sort of the treatment as

1:23:21.120 --> 1:23:25.120
<v Speaker 3>part of the diagnosis, showed that something in that designer

1:23:25.200 --> 1:23:29.120
<v Speaker 3>drug had crossed the blood brain barrier and destroyed the

1:23:29.160 --> 1:23:34.320
<v Speaker 3>substantia nigra. How wow, what was this thing that did this?

1:23:35.640 --> 1:23:41.080
<v Speaker 3>The answer came from yet another unexpected source, a strange

1:23:41.120 --> 1:23:44.320
<v Speaker 3>case study from the nineteen seventies, where a college student

1:23:44.439 --> 1:23:48.040
<v Speaker 3>had used a home chemistry set to make his own drugs,

1:23:48.439 --> 1:23:53.120
<v Speaker 3>namely MPPP, which, like, if I were to tell you

1:23:53.160 --> 1:23:55.519
<v Speaker 3>what that stood for, it would be a lot of

1:23:55.640 --> 1:24:00.439
<v Speaker 3>chemical names that don't mean anything to us, well probably

1:24:00.479 --> 1:24:04.960
<v Speaker 3>to some listeners out there, but yeah not us. Yeah,

1:24:05.160 --> 1:24:10.439
<v Speaker 3>give it a Google. But MPPP, in theory, gives a

1:24:10.560 --> 1:24:16.599
<v Speaker 3>heroin like high. And apparently this college student's experiments worked,

1:24:16.720 --> 1:24:20.160
<v Speaker 3>or at least the first few batches did. A few

1:24:20.160 --> 1:24:24.200
<v Speaker 3>months after starting, he injected himself with a batch and

1:24:24.560 --> 1:24:28.799
<v Speaker 3>immediately felt a burning sensation and within a few days

1:24:29.200 --> 1:24:34.280
<v Speaker 3>lost complete movement, becoming completely immobile and unable to speak.

1:24:35.280 --> 1:24:38.200
<v Speaker 3>And I don't know what happened to this guy, whether

1:24:38.240 --> 1:24:41.840
<v Speaker 3>he eventually received any treatment, but his case eventually made

1:24:41.880 --> 1:24:45.800
<v Speaker 3>it to the NIH, where they discovered that instead of

1:24:45.840 --> 1:24:52.760
<v Speaker 3>making MPPP, he had made something called MPTP, which I

1:24:52.800 --> 1:24:55.240
<v Speaker 3>can name this one out because I have written here

1:24:55.479 --> 1:25:01.320
<v Speaker 3>one methyl for phenal one two three six tetra hydropyridine.

1:25:02.000 --> 1:25:09.320
<v Speaker 3>So yeah, MPTP. Turns out, the chemists that had made

1:25:09.400 --> 1:25:12.440
<v Speaker 3>that designer drug in the nineteen eighties that had paralyzed

1:25:12.439 --> 1:25:16.520
<v Speaker 3>those six people had also been trying to make MPPP

1:25:17.280 --> 1:25:24.519
<v Speaker 3>but instead made MPTP. Okay, those individuals would never be

1:25:24.640 --> 1:25:28.440
<v Speaker 3>the same, never fully recovering from the drug and struggling

1:25:28.479 --> 1:25:32.120
<v Speaker 3>with motor complications for the rest of their lives, many

1:25:32.200 --> 1:25:37.080
<v Speaker 3>of which were shortened. And it's an incredibly tragic story.

1:25:37.920 --> 1:25:40.400
<v Speaker 3>But if one good thing came out of it, it

1:25:40.479 --> 1:25:44.519
<v Speaker 3>was that this situation ended up being a revolution for

1:25:44.600 --> 1:25:49.360
<v Speaker 3>the field of Parkinson's disease research, because with the discovery

1:25:49.400 --> 1:25:53.639
<v Speaker 3>of the effects of MPTP on the brain, researchers now

1:25:53.720 --> 1:25:56.920
<v Speaker 3>had a potential cause for the condition, or could at

1:25:57.000 --> 1:26:01.280
<v Speaker 3>least outline how an environmental contaminant such as an herbicide

1:26:01.320 --> 1:26:04.960
<v Speaker 3>or pesticide could cross the blood brain barrier and cause

1:26:04.960 --> 1:26:10.040
<v Speaker 3>the disease. Secondly, and this is the huge part that

1:26:10.080 --> 1:26:13.520
<v Speaker 3>I started this section with, they could now use MPTP

1:26:13.720 --> 1:26:17.840
<v Speaker 3>to create the first animal models for Parkinson's disease, which

1:26:17.880 --> 1:26:21.200
<v Speaker 3>could be used to test out treatments, study mechanisms, examine

1:26:21.200 --> 1:26:28.600
<v Speaker 3>potential causes. The possibilities were endless. Wow. Yeah. Since the

1:26:28.640 --> 1:26:32.560
<v Speaker 3>discovery of the effects of MPTP, the field of Parkinson's

1:26:32.560 --> 1:26:38.280
<v Speaker 3>disease research has come a tremendously long way. We've learned

1:26:38.520 --> 1:26:41.280
<v Speaker 3>so much more about this disease and how to treat it,

1:26:41.920 --> 1:26:45.160
<v Speaker 3>and this disease has also taught us so much about

1:26:45.200 --> 1:26:50.280
<v Speaker 3>our own brains, unlocking movement pathways and reflexive actions by

1:26:50.320 --> 1:26:53.880
<v Speaker 3>looking at how they break down. We're also in the

1:26:53.920 --> 1:26:57.920
<v Speaker 3>process of reframing this disease by incorporating symptoms that aren't

1:26:57.960 --> 1:27:01.320
<v Speaker 3>movement related, something that is about as we've gotten better

1:27:01.360 --> 1:27:06.040
<v Speaker 3>at diagnosing Parkinson's before the movement symptoms begin, which has

1:27:06.080 --> 1:27:10.839
<v Speaker 3>also allowed people to conduct more precise and accurate clinical trials.

1:27:11.800 --> 1:27:16.280
<v Speaker 3>We're expanding treatment options beyond the narrow dopamine focus, and

1:27:16.520 --> 1:27:20.040
<v Speaker 3>I'm super excited to learn more about those. But I

1:27:20.040 --> 1:27:23.519
<v Speaker 3>think another huge aspect that has really grown in the

1:27:23.560 --> 1:27:27.479
<v Speaker 3>past few decades is the incredible advocacy work done by

1:27:27.479 --> 1:27:30.880
<v Speaker 3>people like Michael J. Fox. There can be such a

1:27:31.000 --> 1:27:37.680
<v Speaker 3>stigma around neurodegenerative diseases, a huge one, including Parkinson's, and

1:27:37.800 --> 1:27:40.599
<v Speaker 3>people like Michael J. Fox and the providers of our

1:27:40.640 --> 1:27:44.719
<v Speaker 3>first hand account who share their experience and are open

1:27:44.760 --> 1:27:49.200
<v Speaker 3>about it, have really done an immeasurable amount of good

1:27:49.280 --> 1:27:54.439
<v Speaker 3>in terms of humanizing this disease. And there's really just

1:27:54.479 --> 1:27:56.479
<v Speaker 3>like so much more that we could talk about in

1:27:56.560 --> 1:28:00.960
<v Speaker 3>terms of Parkinson's. So erin why don't you just cut

1:28:00.960 --> 1:28:02.920
<v Speaker 3>me off here and tell me where we are today

1:28:02.960 --> 1:28:03.759
<v Speaker 3>with this disease.

1:28:04.920 --> 1:28:41.920
<v Speaker 4>I will try to do just that right after this break.

1:28:42.760 --> 1:28:50.240
<v Speaker 4>Parkinson's disease is incredibly common, It is a chronic condition,

1:28:51.360 --> 1:28:56.639
<v Speaker 4>and it is very much on the rise. Yes, both

1:28:56.720 --> 1:29:02.160
<v Speaker 4>the incidents and the prevalence have been increasing across the

1:29:02.200 --> 1:29:07.880
<v Speaker 4>globe for the last several decades. And prevalence listeners may

1:29:08.000 --> 1:29:10.040
<v Speaker 4>or may not recall. I feel like we throw this

1:29:10.080 --> 1:29:14.040
<v Speaker 4>word around a lot. Prevalence is just how many people

1:29:14.360 --> 1:29:17.800
<v Speaker 4>in a population are living with the disease at a

1:29:17.840 --> 1:29:22.880
<v Speaker 4>given time. It makes sense that prevalence is increasing because

1:29:22.920 --> 1:29:27.280
<v Speaker 4>we're living longer. We're an aging global population, and Parkinson's

1:29:27.320 --> 1:29:33.560
<v Speaker 4>disease is predominantly a disease of age. But the incidents,

1:29:33.880 --> 1:29:37.240
<v Speaker 4>or the number of new cases that are diagnosed year

1:29:37.320 --> 1:29:39.920
<v Speaker 4>after year, is also on the rise.

1:29:40.840 --> 1:29:41.759
<v Speaker 3>And this may.

1:29:41.560 --> 1:29:47.960
<v Speaker 4>Be partially but certainly not entirely explained by better diagnostic accuracy,

1:29:48.920 --> 1:29:52.760
<v Speaker 4>especially because Parkinson's seems to be growing faster than other

1:29:52.880 --> 1:29:56.680
<v Speaker 4>neurologic disorders for which we in some cases might have

1:29:56.760 --> 1:30:04.360
<v Speaker 4>better or at least newer diagnostic accuracy, like MS for example. Overall,

1:30:04.439 --> 1:30:07.400
<v Speaker 4>the global burden has more than doubled in the last

1:30:07.560 --> 1:30:12.800
<v Speaker 4>couple of decades, and Parkinson's disease today is often recognized

1:30:12.840 --> 1:30:19.479
<v Speaker 4>as the second most common neurodegenerative disorder after Alzheimer's disease. Okay,

1:30:19.600 --> 1:30:22.800
<v Speaker 4>so it's like Alzheimer's disease and Parkinson's as like the

1:30:22.880 --> 1:30:30.479
<v Speaker 4>two most common neurodegenerative dementia causing diseases. Parkinson's is, of

1:30:30.520 --> 1:30:37.280
<v Speaker 4>course found across the globe. Prevalence is perhaps higher in Europe,

1:30:37.479 --> 1:30:42.840
<v Speaker 4>North America, South America when compared to Africa, Asia, and

1:30:43.240 --> 1:30:46.880
<v Speaker 4>countries in the Middle East. It's really difficult, I think,

1:30:47.000 --> 1:30:49.160
<v Speaker 4>in cases like this to really get a sense of like,

1:30:49.320 --> 1:30:53.320
<v Speaker 4>how true is this versus are places that tend to

1:30:53.320 --> 1:30:59.439
<v Speaker 4>be higher income better at diagnosing this disease unlear But overall,

1:30:59.520 --> 1:31:03.520
<v Speaker 4>this is a disease that is affecting millions and millions

1:31:03.640 --> 1:31:07.080
<v Speaker 4>of people. And like we mentioned in the biology section,

1:31:07.439 --> 1:31:11.759
<v Speaker 4>while Parkinson's disease is not causing death outright, it does

1:31:11.840 --> 1:31:16.720
<v Speaker 4>significantly reduce the length of a person's life, and the

1:31:16.800 --> 1:31:19.880
<v Speaker 4>degree to which that is true varies a lot by

1:31:20.680 --> 1:31:24.519
<v Speaker 4>the time course of the illness. So if we think

1:31:24.600 --> 1:31:29.600
<v Speaker 4>back to dividing Parkinson's into maybe three different subtypes, the

1:31:29.680 --> 1:31:34.040
<v Speaker 4>kind of worse or diffuse malignant group, the intermediate group,

1:31:34.120 --> 1:31:38.960
<v Speaker 4>and the kind of mild motor predominant group, the median

1:31:39.120 --> 1:31:44.000
<v Speaker 4>survival after diagnosis in the diffuse malignant group in some

1:31:44.040 --> 1:31:50.040
<v Speaker 4>studies is only eight years, which is really short, compared

1:31:50.040 --> 1:31:53.960
<v Speaker 4>to thirteen years for the intermediate subtype and twenty for

1:31:54.040 --> 1:31:58.120
<v Speaker 4>a mild motor predominant subtype. Often, when we look at

1:31:58.200 --> 1:32:03.720
<v Speaker 4>just all Parkinson's altogether, the median survival after diagnosis is

1:32:03.800 --> 1:32:08.519
<v Speaker 4>between like six and fourteen years. The good news is

1:32:08.560 --> 1:32:13.000
<v Speaker 4>that there is a lot being done about this disease,

1:32:13.560 --> 1:32:16.360
<v Speaker 4>so much so one of the big hurdles right now

1:32:16.400 --> 1:32:19.880
<v Speaker 4>in Parkinson's disease that we've mentioned a lot is that,

1:32:20.000 --> 1:32:23.280
<v Speaker 4>because this is a clinical diagnosis, you have to have

1:32:23.360 --> 1:32:26.920
<v Speaker 4>these signs and symptoms present, at least some of them

1:32:27.520 --> 1:32:33.759
<v Speaker 4>before somebody can be diagnosed. And these predominantly motor signs

1:32:33.800 --> 1:32:37.720
<v Speaker 4>that are used are not the first signs of neurodegeneration.

1:32:38.360 --> 1:32:39.360
<v Speaker 3>There is this.

1:32:39.439 --> 1:32:44.160
<v Speaker 4>Prolonged, in some cases, very prolonged prodromal period before the

1:32:44.200 --> 1:32:49.200
<v Speaker 4>onset of these symptoms, and that window, first of all,

1:32:49.560 --> 1:32:56.920
<v Speaker 4>neurodegeneration is happening already. So if we can diagnose something earlier,

1:32:57.280 --> 1:33:01.560
<v Speaker 4>we can potentially treat much better because we could potentially

1:33:01.760 --> 1:33:07.400
<v Speaker 4>prevent the progression of disease. Right, So, could we diagnose

1:33:07.439 --> 1:33:13.800
<v Speaker 4>Parkinson's earlier? And can we develop disease modifying treatments that

1:33:13.920 --> 1:33:14.960
<v Speaker 4>actually work?

1:33:15.640 --> 1:33:16.760
<v Speaker 3>So those I.

1:33:16.720 --> 1:33:19.160
<v Speaker 4>Think, in like looking at all of the literature are

1:33:19.200 --> 1:33:24.360
<v Speaker 4>the two biggest areas of research. Can we identify biomarkers

1:33:24.439 --> 1:33:30.200
<v Speaker 4>to diagnose Parkinson's earlier and can we develop disease modifying treatments.

1:33:31.120 --> 1:33:35.679
<v Speaker 4>We've made really big strides and we have so far

1:33:35.760 --> 1:33:38.840
<v Speaker 4>to go. So just this year, a few months ago

1:33:38.960 --> 1:33:41.800
<v Speaker 4>actually maybe a little over a month ago as of

1:33:41.840 --> 1:33:43.600
<v Speaker 4>the time of recording, so by the time this is

1:33:43.640 --> 1:33:46.360
<v Speaker 4>released a few months ago. In the year twenty twenty three,

1:33:47.080 --> 1:33:49.800
<v Speaker 4>a paper came out in Lancet Neurology that was the

1:33:49.840 --> 1:33:54.960
<v Speaker 4>result of this really massive longitudinal study funded in large

1:33:55.000 --> 1:33:58.519
<v Speaker 4>part by the Michael J. Fox Foundation for Parkinson's Research,

1:33:58.920 --> 1:34:02.639
<v Speaker 4>does a huge amount of funding for Parkinson's research, that

1:34:02.880 --> 1:34:07.600
<v Speaker 4>in fact identified a potential biomarker of Parkinson's.

1:34:07.800 --> 1:34:08.720
<v Speaker 3>Ooh.

1:34:08.760 --> 1:34:12.680
<v Speaker 4>What they did was found a way to actually amplify

1:34:12.920 --> 1:34:17.720
<v Speaker 4>and then identify abnormal alpha sin nucleon, that protein that

1:34:17.840 --> 1:34:20.840
<v Speaker 4>makes up the large part of Louis bodies in the

1:34:20.880 --> 1:34:25.719
<v Speaker 4>spinal fluid of people with Parkinson's, including people with only

1:34:25.840 --> 1:34:27.560
<v Speaker 4>prodromal symptoms.

1:34:28.200 --> 1:34:28.760
<v Speaker 3>Wow.

1:34:28.920 --> 1:34:31.839
<v Speaker 4>So they were able to with a lumbar puncture detect

1:34:31.960 --> 1:34:35.320
<v Speaker 4>this abnormal alpha sinnucleon in a way that could predict

1:34:35.360 --> 1:34:39.040
<v Speaker 4>Parkinson's disease that was highly sensitive and specific.

1:34:39.600 --> 1:34:42.240
<v Speaker 3>This is huge. That is huge.

1:34:42.640 --> 1:34:46.240
<v Speaker 4>Yeah, so there is a biomarker.

1:34:46.880 --> 1:34:47.600
<v Speaker 3>Wow.

1:34:48.640 --> 1:34:52.559
<v Speaker 4>This is the first step to having a diagnostic test.

1:34:53.040 --> 1:34:56.519
<v Speaker 4>It is not a diagnostic test. That is the caveat

1:34:56.640 --> 1:34:59.720
<v Speaker 4>This is very very early days. We're not going to

1:34:59.720 --> 1:35:02.760
<v Speaker 4>go around doing lumbar punctures on everyone with constipation, or

1:35:02.800 --> 1:35:05.240
<v Speaker 4>everyone even with a rem sleep disorder or that has

1:35:05.320 --> 1:35:08.840
<v Speaker 4>these prodromal signs or symptoms, and certainly not at the

1:35:08.840 --> 1:35:11.559
<v Speaker 4>point of being able to test, for example, the general

1:35:11.640 --> 1:35:15.080
<v Speaker 4>population or people with a family history or anything like that.

1:35:15.720 --> 1:35:21.200
<v Speaker 4>But this is the kind of breakthroughs in research that

1:35:21.560 --> 1:35:25.360
<v Speaker 4>leads to the potential for these early diagnoses that can

1:35:25.400 --> 1:35:30.520
<v Speaker 4>someday maybe even lead to screening tools that could be available,

1:35:30.560 --> 1:35:37.400
<v Speaker 4>which is incredible. But then with this knowledge, this knowledge

1:35:38.200 --> 1:35:44.080
<v Speaker 4>without a disease modifying therapy doesn't really do anything right.

1:35:44.640 --> 1:35:48.839
<v Speaker 4>So the next step has to be disease modifying therapy

1:35:48.960 --> 1:35:53.120
<v Speaker 4>because otherwise you're diagnosing something very early with nothing that

1:35:53.160 --> 1:35:54.519
<v Speaker 4>you can do to treat it.

1:35:55.439 --> 1:35:58.400
<v Speaker 3>But there's a lot of research.

1:35:58.600 --> 1:36:02.800
<v Speaker 4>Being done on actually finding therapies that could change the

1:36:02.880 --> 1:36:04.280
<v Speaker 4>course of disease.

1:36:05.439 --> 1:36:09.439
<v Speaker 3>It feels maybe this is my bias, but I feel

1:36:09.479 --> 1:36:16.200
<v Speaker 3>like we've been on the precipice of discovering something that

1:36:16.240 --> 1:36:22.559
<v Speaker 3>will halt Parkinson's disease progression for decades. Like it just

1:36:22.640 --> 1:36:26.559
<v Speaker 3>feels like it's just around the corner and just out

1:36:26.560 --> 1:36:30.040
<v Speaker 3>of reach, and like one more study, one more, we

1:36:30.120 --> 1:36:34.120
<v Speaker 3>just need one more transformative breakthrough like we've had so

1:36:34.360 --> 1:36:36.679
<v Speaker 3>often in the history of this disease.

1:36:37.400 --> 1:36:41.479
<v Speaker 4>I think that I agree. I think it's it's so

1:36:41.680 --> 1:36:47.679
<v Speaker 4>disappointing that we're not there yet. I think because there

1:36:47.880 --> 1:36:51.640
<v Speaker 4>have been a lot of studies that have tried a

1:36:51.720 --> 1:36:55.280
<v Speaker 4>lot of different targets, and so far in terms of

1:36:55.439 --> 1:37:00.280
<v Speaker 4>actually halting the progression, there really hasn't been any thing

1:37:00.320 --> 1:37:05.840
<v Speaker 4>that has shown very much promise. There are a lot

1:37:05.880 --> 1:37:09.759
<v Speaker 4>of studies underway. There are drugs that are targeting alphas

1:37:09.800 --> 1:37:14.000
<v Speaker 4>and nucleon There are drugs that are targeting dopamine receptors.

1:37:14.680 --> 1:37:19.560
<v Speaker 4>There are even studies looking into using GLP one agonists,

1:37:19.600 --> 1:37:22.360
<v Speaker 4>which are the drugs that are all the rage right now.

1:37:22.479 --> 1:37:25.280
<v Speaker 4>They were developed as treatment for diabetes. They're also being

1:37:25.360 --> 1:37:28.519
<v Speaker 4>used for weight loss. They're like the drugs that everyone's

1:37:28.520 --> 1:37:28.840
<v Speaker 4>heard of.

1:37:29.320 --> 1:37:30.920
<v Speaker 3>We should do an episode on that.

1:37:31.080 --> 1:37:35.920
<v Speaker 4>Oh, definitely, there's we streched into whether these drugs could

1:37:35.960 --> 1:37:39.560
<v Speaker 4>be beneficial in terms of Parkinson's disease modification.

1:37:40.800 --> 1:37:41.479
<v Speaker 3>There's a lot.

1:37:41.680 --> 1:37:45.000
<v Speaker 4>When I looked at clinicaltrials dot Gov, there are over

1:37:45.080 --> 1:37:48.599
<v Speaker 4>two thousand, six hundred registered clinical trials if you search

1:37:48.640 --> 1:37:53.400
<v Speaker 4>for Parkinson's. Not all of these are drug trials, but

1:37:53.640 --> 1:37:57.080
<v Speaker 4>over twenty three hundred of them are interventional trials of

1:37:57.120 --> 1:38:01.559
<v Speaker 4>some kind, so it's a lot and the third avenue

1:38:01.560 --> 1:38:07.080
<v Speaker 4>of research, in addition to biomarkers identifying disease early and

1:38:07.600 --> 1:38:11.960
<v Speaker 4>disease treatment like changing the course of disease or slowing

1:38:11.960 --> 1:38:16.400
<v Speaker 4>progression of disease, the third very interesting avenue of research

1:38:16.560 --> 1:38:21.800
<v Speaker 4>that is separate but very closely related, is better following

1:38:22.040 --> 1:38:25.680
<v Speaker 4>this disease in terms of clinical progression. So Aarin, you

1:38:25.760 --> 1:38:30.920
<v Speaker 4>sent me an article that was about wearable devices that

1:38:31.160 --> 1:38:34.680
<v Speaker 4>can be used to track the movement of people with

1:38:34.840 --> 1:38:40.800
<v Speaker 4>Parkinson's disease. So these devices in combination with machine learning

1:38:41.320 --> 1:38:46.760
<v Speaker 4>give us better resolution on progression of disease. There's other

1:38:46.800 --> 1:38:51.439
<v Speaker 4>ones that look at speech pattern recognition and deep learning

1:38:51.479 --> 1:38:54.160
<v Speaker 4>and AI machine learning things to be able to track

1:38:54.160 --> 1:38:57.599
<v Speaker 4>the progression of Parkinson's disease in a very nuanced way,

1:38:58.080 --> 1:39:01.639
<v Speaker 4>which is going to be a very important tool when

1:39:01.680 --> 1:39:04.760
<v Speaker 4>we're trying to find disease modifying therapy because if we

1:39:04.800 --> 1:39:08.000
<v Speaker 4>can better parse out what's working and what's not by

1:39:08.080 --> 1:39:11.880
<v Speaker 4>better tracking the progression of this disease, then we're going

1:39:11.920 --> 1:39:13.880
<v Speaker 4>to be able to get a lot better data on

1:39:13.960 --> 1:39:15.479
<v Speaker 4>what's working and what isn't and.

1:39:15.360 --> 1:39:18.879
<v Speaker 3>How yes, I didn't even think about that that aspect

1:39:18.880 --> 1:39:23.280
<v Speaker 3>of it. That's huge for application. Yeah, exactly, exactly. Wow.

1:39:23.600 --> 1:39:28.360
<v Speaker 4>Cool, So there is a lot of hope on the horizon.

1:39:29.080 --> 1:39:32.000
<v Speaker 3>It does, it does feel very hopeful.

1:39:32.280 --> 1:39:32.759
<v Speaker 1>Yeah.

1:39:33.520 --> 1:39:36.800
<v Speaker 3>With that, if you'd like to read more, and there

1:39:36.840 --> 1:39:43.559
<v Speaker 3>is a whole lot more sources, Yeah, I have a bunch,

1:39:43.600 --> 1:39:45.800
<v Speaker 3>but I want to shout out one in particular, and

1:39:45.840 --> 1:39:50.400
<v Speaker 3>it is a book titled Brainstorms, The Race to Unlock

1:39:50.439 --> 1:39:55.000
<v Speaker 3>the Mysteries of Parkinson's Disease by John Paul Ferman. And

1:39:55.479 --> 1:40:00.439
<v Speaker 3>I really really enjoyed this book. The author start to

1:40:00.479 --> 1:40:03.760
<v Speaker 3>write this book because he had gotten to Parkinson's diagnosis

1:40:03.800 --> 1:40:06.880
<v Speaker 3>and it was a really just excellent It was an

1:40:06.920 --> 1:40:11.320
<v Speaker 3>excellent and informative read. Yeah, I recommend. Yeah.

1:40:12.320 --> 1:40:14.840
<v Speaker 4>I have a number of sources as well, but got

1:40:14.880 --> 1:40:17.400
<v Speaker 4>to always shout out whenever the Lancet has a disease

1:40:17.479 --> 1:40:19.919
<v Speaker 4>primer series is just golden.

1:40:20.360 --> 1:40:23.040
<v Speaker 3>Just makes my life so easy. So there was a few.

1:40:23.120 --> 1:40:25.200
<v Speaker 4>There was one from twenty fifteen and then there was

1:40:25.200 --> 1:40:28.519
<v Speaker 4>an update in twenty twenty one. Both are just called

1:40:28.560 --> 1:40:33.559
<v Speaker 4>Parkinson's Disease. They're great, like overall comprehensive reads. There was

1:40:33.920 --> 1:40:37.280
<v Speaker 4>a really interesting paper from twenty twenty two called the

1:40:37.280 --> 1:40:42.000
<v Speaker 4>Neuropsychiatry of Parkinson's Disease, Advances and Challenges from the Lancet Neurology,

1:40:42.439 --> 1:40:45.599
<v Speaker 4>as well as papers on these biomarkers and other research

1:40:45.640 --> 1:40:48.840
<v Speaker 4>being done in terms of treatment. We will post the

1:40:48.880 --> 1:40:51.080
<v Speaker 4>list of sources from this episode in all of our

1:40:51.120 --> 1:40:54.120
<v Speaker 4>episodes on our website This podcast will Kill You dot

1:40:54.160 --> 1:40:56.120
<v Speaker 4>Com under the episode's tab.

1:40:57.200 --> 1:41:00.840
<v Speaker 3>Thank you so much, Stacy for sharing your story with us,

1:41:01.560 --> 1:41:03.360
<v Speaker 3>just truly from the bottom of our hearts.

1:41:03.479 --> 1:41:06.920
<v Speaker 4>Thank you, yeah, so so so much for sharing your

1:41:06.960 --> 1:41:10.840
<v Speaker 4>story with us. Thank you to Bloodmobile for providing music

1:41:10.880 --> 1:41:13.040
<v Speaker 4>for this episode and all of our episodes.

1:41:13.479 --> 1:41:16.439
<v Speaker 3>Thank you to Tom bry Fogel for the audio mixing.

1:41:16.560 --> 1:41:19.639
<v Speaker 3>Thank you, thank you, Thank you to the Exactly Right Network,

1:41:19.840 --> 1:41:22.960
<v Speaker 3>and thank you to you listeners. We hope that you

1:41:23.200 --> 1:41:24.000
<v Speaker 3>learned something.

1:41:24.520 --> 1:41:27.160
<v Speaker 4>Yeah, I'm sure that you did something.

1:41:27.560 --> 1:41:29.200
<v Speaker 3>Yeah.

1:41:29.240 --> 1:41:33.160
<v Speaker 4>And thank you, as always to our patrons. We appreciate

1:41:33.200 --> 1:41:34.760
<v Speaker 4>your support so very.

1:41:34.760 --> 1:41:40.439
<v Speaker 3>Much, so so much. Well, until next time, wash your

1:41:40.479 --> 1:42:07.480
<v Speaker 3>hands you filed the Animals