1 00:00:00,360 --> 00:00:03,880 Speaker 1: Since you're a subscriber to this Bloomberg podcast, we thought 2 00:00:03,880 --> 00:00:07,360 Speaker 1: you'd be interested in a six episode sponsored podcast called 3 00:00:07,800 --> 00:00:12,560 Speaker 1: Targeting the Toughest Diseases produced by Vertex Pharmaceuticals and Bloomberg 4 00:00:12,600 --> 00:00:17,520 Speaker 1: Media Studios. It explores the innovative tools, methods, and unique 5 00:00:17,520 --> 00:00:21,840 Speaker 1: philosophy Vertex Pharmaceuticals is using to search for treatments for 6 00:00:21,880 --> 00:00:29,560 Speaker 1: some of humanity's most challenging diseases. Here's a recent episode. 7 00:00:30,440 --> 00:00:34,240 Speaker 2: Two year olds are a handful. They're full of energy 8 00:00:34,440 --> 00:00:38,120 Speaker 2: and full of laughter. A lot of work for sure, 9 00:00:38,640 --> 00:00:40,520 Speaker 2: but also a source of joy. 10 00:00:43,320 --> 00:00:46,120 Speaker 3: I definitely feel my calling in life was to be 11 00:00:46,159 --> 00:00:48,479 Speaker 3: a mother, and I just feel so blessed to be 12 00:00:48,520 --> 00:00:52,400 Speaker 3: able to have that opportunity to have a child. So 13 00:00:52,440 --> 00:00:53,640 Speaker 3: it's been great. 14 00:00:56,600 --> 00:01:00,280 Speaker 2: That's Rachel Benton, also known as Stetson's. 15 00:00:59,760 --> 00:01:06,240 Speaker 3: Small Stetson is his name, Stetson Corey Benton. I've always 16 00:01:06,560 --> 00:01:10,000 Speaker 3: liked unique names. I never knew of anyone named Stetson before. 17 00:01:11,120 --> 00:01:13,840 Speaker 2: The thing about Stetson is, and he doesn't even know 18 00:01:13,920 --> 00:01:19,560 Speaker 2: this yet, but he may have already saved his mom's life. 19 00:01:20,920 --> 00:01:24,039 Speaker 2: A routine medical test that Rachel only took because she 20 00:01:24,160 --> 00:01:28,160 Speaker 2: was pregnant showed protein in her urine That led to 21 00:01:28,200 --> 00:01:32,440 Speaker 2: further tests, a biopsy, and eventually a phone call delivering 22 00:01:32,440 --> 00:01:35,520 Speaker 2: a diagnosis. It was a. 23 00:01:35,480 --> 00:01:40,479 Speaker 3: Pretty quick conversation. We know it is igiena fhropathy. It's 24 00:01:40,520 --> 00:01:43,560 Speaker 3: a rare kidney disease. There is not a cure. We 25 00:01:43,640 --> 00:01:44,800 Speaker 3: don't have a cause. 26 00:01:46,520 --> 00:01:56,480 Speaker 2: The call was short, but for Rachel it changed everything. Hi. 27 00:01:56,880 --> 00:02:00,360 Speaker 2: I'm Jordan Gospore, a member of the University of Southern 28 00:02:00,360 --> 00:02:05,120 Speaker 2: California's Center for Health Journalism. This is Targeting the Toughest 29 00:02:05,120 --> 00:02:10,560 Speaker 2: Diseases a podcast produced by Bloomberg Media Studios and Vertex Pharmaceuticals. 30 00:02:11,600 --> 00:02:14,600 Speaker 2: In this series, we look at some of humanity's most 31 00:02:14,800 --> 00:02:19,440 Speaker 2: challenging diseases and how Vertex, a Boston based biotech company, 32 00:02:19,919 --> 00:02:24,040 Speaker 2: is using innovative tools, methods, and a unique philosophy to 33 00:02:24,080 --> 00:02:29,519 Speaker 2: search for treatments and cures. Today, we're looking at immunoglobulin 34 00:02:29,600 --> 00:02:35,080 Speaker 2: A nephropathy, more commonly known as IgA nephropathy. It's a 35 00:02:35,120 --> 00:02:39,919 Speaker 2: progressive chronic kidney disease that, for too long, was underreported 36 00:02:40,040 --> 00:02:44,400 Speaker 2: and under researched. We'll talk to experts inside and outside 37 00:02:44,400 --> 00:02:47,240 Speaker 2: of Vertex about the latest work being done in this field, 38 00:02:48,080 --> 00:02:59,120 Speaker 2: But first back to Rachel's story. At the age of thirty, 39 00:02:59,440 --> 00:03:02,880 Speaker 2: Rachel bent and was living a great life. She was 40 00:03:02,919 --> 00:03:06,600 Speaker 2: a licensed mortgage broker running her own agency. She owned 41 00:03:06,639 --> 00:03:10,000 Speaker 2: her own house, and that fall she decided to throw 42 00:03:10,240 --> 00:03:11,800 Speaker 2: a big Halloween. 43 00:03:11,360 --> 00:03:15,600 Speaker 3: Party and he came with one of our mutual friends 44 00:03:15,800 --> 00:03:17,800 Speaker 3: and we sort of rekindled from there. 45 00:03:18,520 --> 00:03:21,880 Speaker 2: He was Tom, a guy she had dated on and 46 00:03:21,919 --> 00:03:23,400 Speaker 2: off during her twenties. 47 00:03:23,200 --> 00:03:26,680 Speaker 3: And then it was the end of November of twenty 48 00:03:26,760 --> 00:03:29,200 Speaker 3: twenty that he asked me to marry him. 49 00:03:29,639 --> 00:03:32,400 Speaker 2: A year later, they got married, and shortly after that, 50 00:03:32,880 --> 00:03:40,000 Speaker 2: Rachel got pregnant. During her pregnancy, Rachel had regular medical checkups, 51 00:03:40,440 --> 00:03:42,080 Speaker 2: including routine yearine tests. 52 00:03:42,680 --> 00:03:45,640 Speaker 3: We did a yearine test, a twenty four hour year 53 00:03:45,680 --> 00:03:48,520 Speaker 3: in test, and that's where you have to take this 54 00:03:48,600 --> 00:03:51,360 Speaker 3: big jug home and you have to peece straight into 55 00:03:51,360 --> 00:03:53,440 Speaker 3: this jug every time for twenty four hours. And so 56 00:03:54,360 --> 00:03:56,960 Speaker 3: I bring it to the doctor and they test it, 57 00:03:57,040 --> 00:03:59,960 Speaker 3: and sure enough, they found protein in my earn. 58 00:04:01,080 --> 00:04:04,360 Speaker 2: The doctor told her she wasn't facing any immediate risk, 59 00:04:04,840 --> 00:04:07,760 Speaker 2: so they agreed to put that result aside, focus on 60 00:04:07,840 --> 00:04:10,960 Speaker 2: having a healthy baby, and that they would investigate further 61 00:04:11,080 --> 00:04:16,680 Speaker 2: once the baby was born Stetson. Corey Benton was born 62 00:04:16,720 --> 00:04:20,440 Speaker 2: in May and as a new parent, Rachel's life instantly 63 00:04:20,480 --> 00:04:21,359 Speaker 2: became a whirlwind. 64 00:04:21,800 --> 00:04:24,520 Speaker 3: Honestly, I completely even forgot about the kidney stuff. 65 00:04:25,160 --> 00:04:27,599 Speaker 2: But around the nine month mark she reached out to 66 00:04:27,600 --> 00:04:32,200 Speaker 2: her doctor. She retested her urine, which confirmed she still 67 00:04:32,279 --> 00:04:35,520 Speaker 2: had protein in her urine, so they decided to do 68 00:04:35,520 --> 00:04:39,120 Speaker 2: a kidney biopsy. A biopsy is where a doctor uses 69 00:04:39,240 --> 00:04:43,039 Speaker 2: a long needle to extract tiny pieces of tissue so 70 00:04:43,080 --> 00:04:46,640 Speaker 2: they can do further tests. Rachel got the results over 71 00:04:46,680 --> 00:04:47,400 Speaker 2: the phone. 72 00:04:49,400 --> 00:04:52,000 Speaker 3: And he's like, you know, we did confirm some things. 73 00:04:52,440 --> 00:04:57,480 Speaker 3: You have a rare kidney disease called IgA nephropathy or 74 00:04:57,560 --> 00:05:02,760 Speaker 3: I GAN. So my fir question was, you know, what 75 00:05:02,920 --> 00:05:05,640 Speaker 3: do I do now? How do I stop this? Is 76 00:05:05,720 --> 00:05:06,360 Speaker 3: there a cure? 77 00:05:06,560 --> 00:05:06,800 Speaker 2: You know? 78 00:05:06,880 --> 00:05:09,520 Speaker 3: Just thinking of anything, like what's the next steps? What 79 00:05:09,560 --> 00:05:10,840 Speaker 3: about medication? Blah blah blah. 80 00:05:10,839 --> 00:05:14,839 Speaker 2: And he's like, well, the answer to almost all of 81 00:05:14,880 --> 00:05:19,920 Speaker 2: her questions was we're not sure or it depends. 82 00:05:21,839 --> 00:05:26,080 Speaker 3: I got off the phone and just cried. I think 83 00:05:26,120 --> 00:05:30,760 Speaker 3: for probably two days straight. I just was overwhelmed with 84 00:05:30,839 --> 00:05:36,480 Speaker 3: obviously the diagnosis and not knowing where this would take 85 00:05:36,520 --> 00:05:39,640 Speaker 3: me in life. What the next You know, twenty four 86 00:05:39,640 --> 00:05:42,560 Speaker 3: hours would look like a year or ten years. You know, 87 00:05:42,800 --> 00:05:44,440 Speaker 3: how is this going to affect me in my day 88 00:05:44,480 --> 00:05:48,320 Speaker 3: to day life and my son and my husband. 89 00:05:51,360 --> 00:05:54,720 Speaker 2: She's adjusted her diet and takes medication to address her 90 00:05:54,760 --> 00:05:58,400 Speaker 2: blood pressure and cholesterol, but the progress of the disease 91 00:05:58,640 --> 00:06:04,680 Speaker 2: is variable. At one point, Rachel's kidney function dropped thirty 92 00:06:04,800 --> 00:06:09,159 Speaker 2: points over two months. The doctor told her that at 93 00:06:09,160 --> 00:06:14,120 Speaker 2: that rate, she'd be needing dialysis within a year. She's rebounded, 94 00:06:14,720 --> 00:06:18,640 Speaker 2: but she doesn't know if that recovery will hold. She 95 00:06:18,680 --> 00:06:23,359 Speaker 2: also deals with fatigue, not just new mom tiredness, but 96 00:06:23,600 --> 00:06:28,760 Speaker 2: debilitating fatigue, where she'll sleep for twelve hours and still 97 00:06:28,920 --> 00:06:32,919 Speaker 2: need a midday nap. In fact, Rachel says that for 98 00:06:32,960 --> 00:06:36,039 Speaker 2: a couple of years before her diagnosis, she was already 99 00:06:36,120 --> 00:06:39,480 Speaker 2: dealing with extreme tiredness, but never really considered it a 100 00:06:39,520 --> 00:06:44,320 Speaker 2: medical condition or something that needed attention. In hindsight, she 101 00:06:44,440 --> 00:06:48,880 Speaker 2: wishes she had gotten it checked out. Looking forward, her 102 00:06:48,920 --> 00:06:51,320 Speaker 2: long term health and her ability to be the kind 103 00:06:51,320 --> 00:06:53,720 Speaker 2: of mom she wants to be is uncertain. 104 00:06:54,880 --> 00:06:57,120 Speaker 3: I have my days where I just feel very, very 105 00:06:57,120 --> 00:07:02,200 Speaker 3: guilty being a other to him with a rare disease 106 00:07:02,360 --> 00:07:06,640 Speaker 3: and not knowing in a year, ten years, however long, 107 00:07:07,080 --> 00:07:10,560 Speaker 3: how I'm going to be and how active I get 108 00:07:10,560 --> 00:07:13,120 Speaker 3: to be in his life. Every day. I just try 109 00:07:13,120 --> 00:07:15,000 Speaker 3: to make the best of it though, and you know, 110 00:07:15,120 --> 00:07:17,320 Speaker 3: whatever he wants to do, I put on a smile 111 00:07:17,360 --> 00:07:18,880 Speaker 3: and try to push. 112 00:07:18,680 --> 00:07:26,680 Speaker 2: Through immunoglobulin A nephropathy or IGAN. It's not a high 113 00:07:26,720 --> 00:07:31,560 Speaker 2: profile disease. It's a pronic kidney disease that historically has 114 00:07:31,640 --> 00:07:34,720 Speaker 2: not been well understood, but that's changing. 115 00:07:35,600 --> 00:07:39,120 Speaker 4: So I do clinics, so I see patients with gramariala disease. 116 00:07:39,760 --> 00:07:42,800 Speaker 4: I run clinical trials, and I have my research work 117 00:07:42,920 --> 00:07:44,440 Speaker 4: at the university and the laboratory. 118 00:07:46,560 --> 00:07:49,920 Speaker 2: That's doctor Jonathan Barrett. He's based at the University of 119 00:07:50,000 --> 00:07:52,640 Speaker 2: Leicester in England and as a world renowned leader in 120 00:07:52,720 --> 00:07:53,480 Speaker 2: kidney research. 121 00:07:54,600 --> 00:07:57,520 Speaker 4: So most of my career, no one was really interested 122 00:07:57,520 --> 00:08:01,120 Speaker 4: in Nigeria property apart from a few people. Now it 123 00:08:01,160 --> 00:08:03,120 Speaker 4: is you can't move at a kidney meeting without people 124 00:08:03,120 --> 00:08:04,360 Speaker 4: talking about igenafropathy. 125 00:08:05,080 --> 00:08:07,800 Speaker 2: One reason it was so under researched is that in 126 00:08:07,840 --> 00:08:11,040 Speaker 2: the early stages, symptoms are often hard to detect. 127 00:08:11,520 --> 00:08:14,600 Speaker 4: Normally, the patients I see have no idea why they're 128 00:08:14,600 --> 00:08:15,760 Speaker 4: coming to see a kidney doctor. 129 00:08:16,160 --> 00:08:20,000 Speaker 2: In many cases, it starts with an asymptomatic person having 130 00:08:20,040 --> 00:08:23,440 Speaker 2: a urine test, like in Rachel's case, with a routine 131 00:08:23,560 --> 00:08:24,840 Speaker 2: urine test during pregnancy. 132 00:08:25,080 --> 00:08:27,280 Speaker 4: Perhaps you've joined a new gym, you get a physical, 133 00:08:27,320 --> 00:08:29,680 Speaker 4: so you want to get a mortgage. You might have 134 00:08:29,760 --> 00:08:32,640 Speaker 4: a job that requires you to have a physical and 135 00:08:32,720 --> 00:08:34,800 Speaker 4: someone dips your urine and they don't wait a minute, 136 00:08:34,840 --> 00:08:36,160 Speaker 4: there's blood and protein in here. 137 00:08:37,040 --> 00:08:38,720 Speaker 2: Here's what we do know about the disease. 138 00:08:40,720 --> 00:08:43,560 Speaker 4: So each kidney contains about a million filters and they 139 00:08:43,559 --> 00:08:47,360 Speaker 4: are continually filtering the blood to generate the urine, and 140 00:08:47,440 --> 00:08:52,000 Speaker 4: in igenafropathy, this protein called IgA starts sludging up those 141 00:08:52,040 --> 00:08:56,360 Speaker 4: filters and stopping them from working properly. And if the 142 00:08:56,400 --> 00:09:01,079 Speaker 4: filters don't work very well, they become leaky and blood 143 00:09:01,120 --> 00:09:02,679 Speaker 4: and protein can appear in the urine. 144 00:09:03,800 --> 00:09:08,760 Speaker 2: Over time, sometimes months, sometimes years, your kidney function declines. 145 00:09:10,080 --> 00:09:13,200 Speaker 4: Some patients do really well with igenafropathy, and others end 146 00:09:13,280 --> 00:09:15,840 Speaker 4: up on dialysis relatively quickly. And that's the bit we 147 00:09:15,840 --> 00:09:17,240 Speaker 4: haven't quite worked out yet. 148 00:09:18,400 --> 00:09:21,200 Speaker 2: In fact, we know the majority of adult patients with 149 00:09:21,280 --> 00:09:26,080 Speaker 2: igaafhropathy will progress to instage kidney disease, which requires them 150 00:09:26,160 --> 00:09:29,640 Speaker 2: to go on dialysis or get a transplant within twenty 151 00:09:29,720 --> 00:09:34,040 Speaker 2: years of diagnosis. Doctor Barrett says there is evidence of 152 00:09:34,080 --> 00:09:37,680 Speaker 2: a genetic component, but the connections aren't strong enough to 153 00:09:37,679 --> 00:09:42,240 Speaker 2: do genetic screening right now. The only way to diagnose 154 00:09:42,280 --> 00:09:44,720 Speaker 2: iganaphropathy is with the kidney biopsy. 155 00:09:45,720 --> 00:09:48,800 Speaker 4: But what we think is that the major driver for 156 00:09:48,840 --> 00:09:53,160 Speaker 4: this disease is the type of ida we normally produce 157 00:09:53,200 --> 00:09:55,920 Speaker 4: in our gut and in our respiratory tract that normally 158 00:09:55,920 --> 00:09:59,480 Speaker 4: gets into our sputum, into our tears, into our saliva. 159 00:10:00,000 --> 00:10:02,000 Speaker 4: It's there to stop bugs entering the body, and it 160 00:10:02,000 --> 00:10:04,720 Speaker 4: does a very very good job. But in igenic property, 161 00:10:04,840 --> 00:10:07,679 Speaker 4: some of that ida actually gets into the bloodstream. When 162 00:10:07,679 --> 00:10:10,440 Speaker 4: it's in the bloodstream, it's a bit out of place, 163 00:10:10,960 --> 00:10:13,200 Speaker 4: and it tends to stick to itself, to stick to 164 00:10:13,240 --> 00:10:16,920 Speaker 4: other proteins. There are antibodies in the circulation it sticks to, 165 00:10:17,360 --> 00:10:20,160 Speaker 4: and that forms these large what we call immune complexes, 166 00:10:20,200 --> 00:10:25,120 Speaker 4: which are essentially big aggregates of protein. If you've got 167 00:10:25,160 --> 00:10:27,440 Speaker 4: big globs of protein, it's completely reasonable to think that 168 00:10:27,440 --> 00:10:30,040 Speaker 4: those globs approtein are going to start clogging up the filter, 169 00:10:30,600 --> 00:10:33,040 Speaker 4: which is exactly what happens, and when they clog up 170 00:10:33,040 --> 00:10:37,439 Speaker 4: the filter, there's inflammation, they're scarring, and that's what eventually 171 00:10:37,480 --> 00:10:39,000 Speaker 4: causes kidney failure. 172 00:10:39,360 --> 00:10:43,600 Speaker 2: For people diagnosed with IgA nefhropathy. The biological effects are 173 00:10:43,640 --> 00:10:45,199 Speaker 2: only part of the problem. 174 00:10:45,679 --> 00:10:49,280 Speaker 4: The big challenge is actually the impact on mental wellness. 175 00:10:49,600 --> 00:10:53,320 Speaker 4: Because if you're a young person and I tell you 176 00:10:53,320 --> 00:10:57,240 Speaker 4: you've got this disease, it's incurable. There's a risk it 177 00:10:57,240 --> 00:10:59,280 Speaker 4: could cause kidney failure in the future, but I can't 178 00:10:59,280 --> 00:11:01,520 Speaker 4: tell you when you might need to go on diallasis 179 00:11:01,559 --> 00:11:03,480 Speaker 4: have you get your transplant, but I can't tell you when. 180 00:11:03,960 --> 00:11:08,720 Speaker 4: That sense of uncertainty can be absolutely devastating for young people. 181 00:11:08,760 --> 00:11:11,720 Speaker 4: You imagine developing your career, wanting to pay that big 182 00:11:11,720 --> 00:11:14,600 Speaker 4: amount of money for a house, getting married, thinking about children, 183 00:11:15,000 --> 00:11:17,600 Speaker 4: and you have this threat hanging over you of a 184 00:11:17,600 --> 00:11:21,400 Speaker 4: disease that the doctors can't really predict. 185 00:11:25,320 --> 00:11:29,120 Speaker 2: Addressing that fear and uncertainty requires showing patients there is 186 00:11:29,200 --> 00:11:32,160 Speaker 2: a way forward, and that's what the team at Vertex 187 00:11:32,280 --> 00:11:39,240 Speaker 2: is doing. Igienephropathy represents exactly the kind of medical problem 188 00:11:39,360 --> 00:11:42,599 Speaker 2: Vertex is targeting. There's a long history of research to 189 00:11:42,640 --> 00:11:46,520 Speaker 2: build on there's new technology available or Vertex thinks they 190 00:11:46,520 --> 00:11:49,960 Speaker 2: can develop it. There's a large unmet need, and Vertex 191 00:11:50,040 --> 00:11:53,439 Speaker 2: thinks it may be possible to tackle the underlying disease. 192 00:11:55,679 --> 00:11:59,080 Speaker 5: Simply put, Verticy's goal is to help people suffering from 193 00:11:59,160 --> 00:12:01,920 Speaker 5: serious diseases, and we do that by investing in the 194 00:12:01,960 --> 00:12:04,760 Speaker 5: scientific innovation to create what we believe could be truly 195 00:12:04,760 --> 00:12:06,959 Speaker 5: transformative medicines for people with these diseases. 196 00:12:07,679 --> 00:12:10,880 Speaker 2: That's Mark Bunnage. He's the head of research at Vertex 197 00:12:10,920 --> 00:12:15,400 Speaker 2: Pharmaceuticals and leads research on the company's pipeline of serious diseases. 198 00:12:16,520 --> 00:12:18,880 Speaker 5: Now, we focus on cause of human biology and on 199 00:12:18,960 --> 00:12:22,200 Speaker 5: human validated targets, and then we ask the question what's 200 00:12:22,240 --> 00:12:26,160 Speaker 5: the right approach to take, and we are completely metalitiagnostic. 201 00:12:27,080 --> 00:12:29,240 Speaker 5: We'll use whatever is the right tool in the toolbox 202 00:12:29,240 --> 00:12:32,000 Speaker 5: if you like, to address their biology and then to 203 00:12:32,000 --> 00:12:36,880 Speaker 5: come up with a transformative therapy. 204 00:12:37,960 --> 00:12:42,800 Speaker 2: Earlier, doctor Barrett explained how igianophropathy occurs. It's a build 205 00:12:42,880 --> 00:12:45,920 Speaker 2: up of what he calls big globs of protein that 206 00:12:45,960 --> 00:12:49,240 Speaker 2: deposit and cause injury to the filters in your kidneys. 207 00:12:50,360 --> 00:12:53,360 Speaker 2: But how can we stop that from happening. To answer that, 208 00:12:53,800 --> 00:12:57,120 Speaker 2: I sat down with doctor Maniche Maski. He's a board 209 00:12:57,160 --> 00:13:03,240 Speaker 2: certified nephrologist helping lead Vertex research into IgA nephropathy. Doctor 210 00:13:03,320 --> 00:13:06,760 Speaker 2: Maski explained that B cells, an important part of our 211 00:13:06,760 --> 00:13:10,280 Speaker 2: immune system to fight off infections, can lose control and 212 00:13:10,400 --> 00:13:14,240 Speaker 2: produce antibodies that hurt our own organs, in this case, 213 00:13:14,400 --> 00:13:19,400 Speaker 2: the kidneys. Can you tell us a little bit about 214 00:13:19,440 --> 00:13:21,840 Speaker 2: where the field is going and what's being done for 215 00:13:21,920 --> 00:13:23,800 Speaker 2: people living with IgA nephropathy. 216 00:13:24,400 --> 00:13:28,880 Speaker 6: Absolutely, we now understand that loss of B cell control 217 00:13:29,760 --> 00:13:35,000 Speaker 6: is what leads to the downstream mechanisms resulting in kidney 218 00:13:35,000 --> 00:13:39,240 Speaker 6: injury and kidney function loss. So lots of research has 219 00:13:39,280 --> 00:13:43,920 Speaker 6: been performed to try to understand what is influencing the 220 00:13:43,960 --> 00:13:47,960 Speaker 6: B cell to lose control. It turns out that two 221 00:13:48,000 --> 00:13:53,239 Speaker 6: proteins called Bath and april are key drivers. 222 00:13:57,400 --> 00:14:00,520 Speaker 2: Okay, so B cells are a type of white blood 223 00:14:00,559 --> 00:14:04,000 Speaker 2: cell that helps power our immune system. Can you tell 224 00:14:04,040 --> 00:14:06,560 Speaker 2: us a little bit more about what Bath and April 225 00:14:06,600 --> 00:14:09,080 Speaker 2: are and how they're involved in B cell control and 226 00:14:09,120 --> 00:14:11,400 Speaker 2: how all that relates to iganephropathy. 227 00:14:12,520 --> 00:14:17,280 Speaker 6: So, first, Jordan, you're absolutely right that B cells, when 228 00:14:17,320 --> 00:14:21,160 Speaker 6: they're doing what they're supposed to do, protect us from infections. 229 00:14:21,600 --> 00:14:25,040 Speaker 6: They make cand of bodies that help us neutralize various pathogens. 230 00:14:26,200 --> 00:14:30,520 Speaker 6: When B cells lose control, they can set off a 231 00:14:30,840 --> 00:14:36,200 Speaker 6: cascade of events that result in processes that harm the body, 232 00:14:36,320 --> 00:14:42,840 Speaker 6: so called autoimmune diseases. Bath and April are two similar 233 00:14:43,120 --> 00:14:47,960 Speaker 6: but distinct proteins that control the life cycle of the 234 00:14:48,000 --> 00:14:52,160 Speaker 6: B cell. So bath more in the early stage of 235 00:14:52,760 --> 00:14:55,440 Speaker 6: development and maturation of the B cell and april more 236 00:14:55,480 --> 00:14:59,120 Speaker 6: in the later stage of the B cell development all 237 00:14:59,120 --> 00:15:02,440 Speaker 6: the way through to becoming an antibody secreting cell. Bath 238 00:15:02,480 --> 00:15:07,160 Speaker 6: in april really seem to be two of the most 239 00:15:07,200 --> 00:15:12,520 Speaker 6: critical proteins driving this transition from something that would protect 240 00:15:12,600 --> 00:15:17,480 Speaker 6: us to something that would actually make antibodies that will 241 00:15:17,760 --> 00:15:19,080 Speaker 6: harm our native tissues. 242 00:15:21,120 --> 00:15:25,160 Speaker 2: This is a complex scenario. What's the innovative thinking that 243 00:15:25,280 --> 00:15:26,760 Speaker 2: Vertex is considering here. 244 00:15:27,840 --> 00:15:31,040 Speaker 6: We know that the levels of bath in april are 245 00:15:31,040 --> 00:15:34,440 Speaker 6: actually elevated in people with ig and ephropathy, and that 246 00:15:34,480 --> 00:15:38,160 Speaker 6: these levels correlate with measures of kidney function and damage. 247 00:15:38,320 --> 00:15:41,080 Speaker 6: So through that we believe both of these drivers are 248 00:15:41,160 --> 00:15:44,560 Speaker 6: involved in uncontrolled B cells. Not Bath alone and not 249 00:15:44,680 --> 00:15:47,480 Speaker 6: april alone. There's a need to cast the widest net 250 00:15:47,680 --> 00:15:51,960 Speaker 6: to catch the main actors involved in the pathogenesis of 251 00:15:52,000 --> 00:15:55,240 Speaker 6: IgA and nephropathy. What we hope to see with this 252 00:15:55,280 --> 00:15:59,320 Speaker 6: approach is the potential to restore immune balance for our 253 00:15:59,360 --> 00:16:04,080 Speaker 6: patients and give them the best chance at remission in 254 00:16:04,120 --> 00:16:06,960 Speaker 6: the protin area, which is the protein spilling in the 255 00:16:07,080 --> 00:16:10,000 Speaker 6: urine he maturia, which is the spilling of blood in 256 00:16:10,040 --> 00:16:13,880 Speaker 6: the urine with associated stabilization of kidney function. 257 00:16:16,920 --> 00:16:21,560 Speaker 2: For Rachel Benton, living with uncertainty has become a constant burden. 258 00:16:23,560 --> 00:16:27,760 Speaker 3: It really scares me. For my son, I feel like 259 00:16:27,800 --> 00:16:30,560 Speaker 3: I let him down. I guess, you know, it's not 260 00:16:30,800 --> 00:16:33,720 Speaker 3: fair for him to have a mom that is going 261 00:16:33,800 --> 00:16:35,840 Speaker 3: to be sick for the rest of our life. It 262 00:16:35,920 --> 00:16:38,960 Speaker 3: might not be bad today, but we don't know about tomorrow, 263 00:16:39,120 --> 00:16:41,960 Speaker 3: you know. And I just I feel guilt in that 264 00:16:42,040 --> 00:16:46,240 Speaker 3: aspect of him just not having a healthy mom. Same 265 00:16:46,320 --> 00:16:48,920 Speaker 3: for my husband, for him to have a wife that 266 00:16:49,040 --> 00:16:52,800 Speaker 3: just doesn't healthy and it breaks my heart for them really. 267 00:16:54,360 --> 00:16:56,760 Speaker 3: But I try to stay positive and take care of 268 00:16:56,760 --> 00:16:59,880 Speaker 3: myself as much as I can, but it definitely does 269 00:17:00,120 --> 00:17:04,640 Speaker 3: play a huge role on your mental health for sure. 270 00:17:04,840 --> 00:17:05,400 Speaker 2: Day to day. 271 00:17:05,920 --> 00:17:07,840 Speaker 3: Some days I can be like, you know what, I 272 00:17:07,880 --> 00:17:11,400 Speaker 3: am a warrior I got this. Everything's great. In other 273 00:17:11,480 --> 00:17:15,280 Speaker 3: days it's like I am not okay, and I feel 274 00:17:15,280 --> 00:17:17,520 Speaker 3: like I could just crawl under a rock and stay there. 275 00:17:18,320 --> 00:17:21,480 Speaker 2: Rachel, like a lot of people living with IgA nephropathy, 276 00:17:21,920 --> 00:17:25,080 Speaker 2: has become an advocate, encouraging others to get checked. 277 00:17:25,840 --> 00:17:28,560 Speaker 3: All of my friends because of this, I'm like, please 278 00:17:28,720 --> 00:17:31,720 Speaker 3: get your yearlys done, but also ask for that urine test. 279 00:17:32,359 --> 00:17:34,919 Speaker 3: You know, if you see any sign of protein in 280 00:17:34,960 --> 00:17:37,240 Speaker 3: your urine, just double check it. Why not? 281 00:17:38,560 --> 00:17:43,520 Speaker 2: Exactly why not? Kidney health is not top of mind 282 00:17:43,520 --> 00:17:46,639 Speaker 2: for most people, but it's worth talking to your doctor about. 283 00:17:47,520 --> 00:17:51,680 Speaker 2: You can also go to Vertex's website vrtx dot com 284 00:17:51,720 --> 00:17:55,760 Speaker 2: for more information on Vertex's commitment to IgA nephropathy and 285 00:17:55,840 --> 00:18:02,760 Speaker 2: other serious kidney diseases. This is Targeting the Toughest Diseases 286 00:18:03,160 --> 00:18:07,760 Speaker 2: a podcast from Bloomberg Media Studios and Vertex Pharmaceuticals. If 287 00:18:07,800 --> 00:18:10,439 Speaker 2: you like what you hear, subscribe and leave us a review. 288 00:18:11,200 --> 00:18:13,640 Speaker 2: I'm Jordan Gospore. Thanks for listening.