Race to Cure Life-Threatening Skin Disease May Be Key to Help Others

PAULA NEWTON: So, this week marks Rare Disease Day. Shining a light on the battle one in 10 people endure globally against illnesses that are often incurable and understudied. And one of those rare illnesses is Epidermolysis Bullosa or EB. A genetic skin disease that causes blistering, leaving patients to live constantly wrapped up in bandages. The lives of EB patients are the focus of a new documentary now streaming on Netflix entitled “Matter of Time.” Hari Sreenivasan speaks to EB experts Dr. Jean Tang and Michael Hund about the struggle and the resilience of those grappling with this condition.

 

HARI SREENIVASAN: Paula, thanks so much. Dr. Jean Tang and Michael Hund, thank you both for joining us. Dr. Tang, I wanna start with you. You’re a professor of dermatology at Stanford University and you are focused on rare genetic skin diseases, including Epidermolysis Bullosa, the skin disease that’s featured in this documentary. And first of all, I guess, what is it? What does it do to people?

 

JEAN TANG: Epidermolysis Bullosa or EB, it’s a genetic skin disease. It’s very rare, thankfully. But these unfortunate patients inherit a genetic mutation where it’s a single genetic letter change that makes the difference between me and you and them with fragile skin that’s often wounded, painful – many of them can’t go to school, can’t run, can’t play soccer, and can’t have a normal quality of life that a child deserves because of this single one genetic mutation.

 

SREENIVASAN: And what’s happening to their skin?

 

TANG: Right. So the genetic mutation changes a protein, so the protein doesn’t, isn’t able to staple the top layer of your skin to the bottom layer of your skin. So with any gentle friction or trauma, the skin shears apart and their blisters and their wounds, and these kids are covered in wound dressings from head to toe to try to protect their skin.

 

SREENIVASAN: Michael, the film is called “Matter of Time,” and I watched it, you know, partly because I am a child of the nineties from Seattle, and I said, Oh my gosh, Eddie Vedder from Pearl Jam is involved in something. Let me find out more, right? So I’m watching this, what could be a concert video. But in between you see how committed he and his wife Jill have been to trying to figure out a cure for EB. What motivated them in the first place?

 

MICHAEL HUND: Yeah, so, so Jill and Ed are Herculean, right? What they’ve given and their leadership, their platform, shining a light on this community. And really the inspiration, Hari, was Jill had a childhood friend who had a son with Epidermolysis Bullosa. And you know, what we hope the film conveys is when you meet someone with EB, you quickly learn a lot about bravery and courage and resilience. And certainly it had that impact on Jill and Ed, and they said, look, you know, we’ve got a platform. We’ve got a voice, we’ve got a stage. Let’s shed a light on this community. 

We started with, with funding a handful of researchers that’s expanded to 200 projects in 22 different countries, $80 million raised across the planet. We’ve gone from two clinical trials to now more than 50 clinical trials. And most importantly, in the last two years alone, thanks to brilliant folks like Dr. Jean Tang, we’ve seen three FDA approvals for Epidermolysis Bullosa, which gives us hope, because if you think about EB, it’s one of 10,000 or more rare diseases — 400 million people on the planet, yet 95% don’t yet have any FDA approved treatments. We’ve done that, you know, three times in the last two years. But those treatments — ultimately we want to cure. So that’s the goal.

 

SREENIVASAN: Dr. Tang, there are several kind of stories in here of different people, different patients of different ages, and what they’re going through. And one is of Rowan Holler. 

 

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SREENIVASAN: Tell us how do children like Rowan get through the day? What are the acts that their caregivers, their parents, have to perform to try to just get by? 

 

TANG: So the day-to-day life of a family with a child with EB is one where — probably in the morning, you know, the child wakes up. You have to think about soft foods, because difficult to eat foods like chips or anything hard will tear the inside skin of their mouth. And they have problems swallowing. So oftentimes the food has to be soft. Then you’re basically wrapping the skin to protect it. And sometimes the worst event happens later in the day, in the evening. And usually these kids need a bath and a wound dressing change every day or every other day. And it feels like, you know, the parent is torturing the child, ‘cause as a young child, you don’t know the consequences, right? All you’re saying to the parents is, I don’t want this. I don’t wanna take the bandages off. It hurts. And so there’s a lot of negotiation and you know, as a parent, I just think about that kind of daily struggle and ordeal and the amount of strength and creativity that a family must have to be able to basically walk this difficult journey every single day of their life.

 

SREENIVASAN: Michael Hund, the approach that you are taking is a venture philanthropy model. I guess, for our audience, explain what that is, what the benefits are compared to a traditional model, and whether that has been the sort of key to unlocking these, you know, three different FDA approvals and so forth.

 

HUND: You know, bold missions require innovative business models. And, and so we’ve always believed that while we’re a nonprofit organization focused on medical research for EB, that the community deserves for us to run a really good business. And, and what that looks like for us is venture philanthropy. So, what does venture philanthropy mean? That means that every penny that we invest in research has an upside in which, if that science and research is commercialized, a return comes back to the foundation to reinvest in more research, until ultimately we have more treatments and a cure. And really, Hari, this creates a sustainable fundraising model. If somebody gives us a dollar, we can turn that dollar into $6.

It also solves, you know, a big market problem that is not completely unique to rare disease, which is what we call the Valley of Death in medical research. (08:57) You know, most science struggles to get out of a brilliant lab like Dr. Tang’s into a commercial setting of a biotech or pharmaceutical company to go through the phases of clinical trials and ultimately get a regulatory approval. But we also believe that it can help many, many other rare diseases as a model that can be scaled.

 

SREENIVASAN: Yeah. Michael, this film was so wonderful in kind of opening the audience up to the personal lives, — even a small glimpse of the lives of some of the individuals that are affected by this and their families. One of them was Deanna Molinaro. Tell us a little bit about Deanna. She tragically passed at 31 years of age, while most people with EB might die far sooner, right? What moved you about her and the time that you knew her?

 

HUND: Well, Deanna was a force, a giant, a hero. And, you know, you, you hear in the film pretty profound things that Deanna says. And, one of them that always sticks with me is that she says, you know, I’ve learned that life is about the quality, not the quantity of the years. And the attitude and mentality that she brought to her life every day, despite the challenges that she faced, despite the burden that EB placed on her, She greeted each day with positivity, with joy, with fire in her belly, with art, with music. And, you know, if you, if you get an opportunity look at Deanna’s art because it reminds us of, of who she is and how she expressed herself. Listen to Deanna’s words. 

You know, one of the most powerful scenes in the film to me is when she’s sitting with Rowan and they’re doing makeup together before going to the show. You know, and it’s this moment of you’ve got these two young women, that were dealt the same gene, you know, at birth. (29:44) And Deanna knows that Rowan’s life will be improved because of the work of people like Dr. Jean Tang because of the work that our foundation has been able to invest in across the planet. But she also knew how important her time with Rowan was to really be that mentor, to be that friend. 

 

SREENIVASAN: Dr. Tang, with the help of this program, this partnership you have been able to see in this particular case, three FDA-approved treatments. It’s not quite a cure. But what do these treatments do for different kinds of EB that exist?

 

TANG: Right. So all of these treatments wouldn’t have happened without the patient foundation. So EB is one of the worst diseases you’ll ever hear about. But we’re fortunate because we have the power of, you know, wonderful patron saints like Eddie Vedder and the foundation to fund this kind of research. There’s absolutely no way that federal government money and grants would’ve brought us here. 

So in terms of the FDA approved treatments, what are they? These are topical treatments that try to heal existing wounds, close them, heal them, so the child feels less pain, less itch. And they are disease modifying, they’re definitely helping the patients. They’re FDA approved. The one that I worked on at Stanford is one where we biopsy the patient’s skin cells, use a virus and put in the wild type correct gene. And then sew on the genetically corrected patient cells onto their wounds to heal their skin. 

Oftentimes these medicines are costly because there aren’t a lot of patients, right? So as scientists, we’re really thinking about how to make this scalable. How do we deliver a technology and a medicine that can be given to patients wherever they live, and at a price where it’s not gonna bankrupt insurance? These are all hard questions.

 

SREENIVASAN: I mean, what you’re describing is almost a layer of precision in medicine that I haven’t heard of and seen before. Is this enabled by sort of CRISPR technology that we’ve heard about over the last few years? Or again, how do you do this for a hundred or a thousand or 10,000 patients with, you know — to make sure that the medicine works for each of them?

 

TANG: It’s a great question. So, the FDA-approved drugs use viruses currently to insert the entire Collagen VII gene into the patient’s cells. So now the patient cells are able to bind to the bottom of the skin layer and the wounds will heal. That process is cumbersome. It takes a long time. And now with CRISPR gene editing things can be different. 

One challenge is that many of these patients have different mutations, right? And so I believe NPR reported this and others, but FDA created a new mechanism and guidance called the plausible mechanism. And so the idea with CRISPR gene editing is, Look, I’ve got the reagents to correct patient one, mutation one. Most of the reagents are gonna be the same between patient one and patient two. And so maybe the regulatory burden, the toxicology studies, the experiments that one has to do to put this in humans for mutation two, mutation three, mutation four, is going to be easier and quicker. And that is a specific way in which gene editing medicine, precision medicine, can be scaled faster and cheaper.

 

SREENIVASAN: Dr. Tang just for clarification, what is the threshold for a definition of a rare disease? I mean, I know that the end of this month, February 28th, is Global Rare Disease Day. But what do we kind of mean when we say that?

 

TANG: Right. The government’s definition of what qualifies as a rare disease is a disease where there’s less than 200,000 people in the world. And so if you add up all the different types of rare diseases, it’s not so rare, but the individual mutation such as EB, it is rare. And I’m so glad that there is a Rare Disease Day just to raise awareness and, and tell people more about the patients, the families, their need. 

But I feel like this documentary and all the people that are part of it, I mean, they deserve an Olympic medal. Because the artists the musicians, the creative filmmakers the fundraisers, the patients families, I mean, it’s a story of hope that will bring, you know, science and success out to the public — and leave it to the artists and the creative people to tell the humanitarian story that sometimes scientists like myself aren’t quite able to convey.

 

SREENIVASAN: I mean, when you look at diseases, it seems that if there’s not a celebrity attached, it’s almost like a Hunger Games or survivor competition where you have this finite resource and you have all these rare diseases and these families kind of competing for it. And, I don’t know, you know, you’ve been in this space for a while and I hate to be kind of cynical about it that way, but it just seems like that’s not every disease is kind of getting its day in the sun.

 

HUND: I do think one of the solutions for rare disease is as much as we can go it together. Because again, in isolation, these disease are exactly that. They are rare. But when you look at the cohort and aggregate of all of those living with a rare disease, I mean, that’s one in 10 people on the planet affected by a rare disease that’s more than cancer and HIV combined. (23:19) So, so this is a big cohort of those living with rare disease. 

Something that we focus on and we’re interested in is, yes, every rare disease might not have a celebrity ambassador. However, most rare diseases face the same challenges. You know, funding for research, recruiting for clinical trials, having awareness, having a voice, and look — things like a rare disease day help. But for us, how can we take a model that works, that’s certainly benefited from people like Jill and Eddie Vedder, but how can we share that, how can we come together as a community and unite as a rare disease community and share those successes, share those benefits from fundraising to models, to research, to scalable now technologies that we have in medicine, as you hear Dr. Tang talk about, you know, the gene editing. I mean, these are things that are transferrable and scalable.

 

SREENIVASAN: Dr. Tang, similar question to you. I mean, is there a method or a process that you can see going from EB to other rare diseases and where you can inform other researchers, say, here’s what I did, here’s what is published, here’s what you can recreate.

 

TANG: Absolutely. The gene editing field is incredible. And I know Jennifer Doudna was on your show and explained CRISPR gene editing and discovered it. The challenge is it’s working in the lab and in terms of drug approvals and drugs getting to the patients, it’s very few. And so any gene editing program, any clinical trial with regulatory interactions with the FDA, that will set an important precedence for all the other gene editing drugs and whatever, different diseases. So any progress, any rules, any precedence you set with the FDA will help all the programs. What is the quality of the reagent of the RNA? How many patients does it take to see an FDA approval? How long do we have to follow the patients for safety, right? So the more we’re able to progress in EB, I know it will help all the other rare genetic diseases.

 

SREENIVASAN: You know, Dr. Tang, recently the administration had cut back on about $9 billion worth of grants for the National Institutes of Health. That was about 2,600 different research grants, I think. And I don’t know if directly EB was affected, but I wonder how has this end of funding affected the landscape of the research that you and your colleagues are doing into rare diseases?

 

TANG: All I can say is the cuts are terrible, and the landscape has changed. We are having a hard enough time convincing Americans to go into science. And with this kind of funding cut and the desperation for research dollars, it basically is a dark cloud all over science. In terms of the gene editing technology — that was directly funded by the NIH. So think about for the next, you know, three to four years with these cuts in science funding, what other research technologies are we potentially missing on that are game breaking? Who are the young scientists and the labs that we aren’t able to support? 

And as I said before, there is no way that these FDA-approved drugs for EB would’ve happened without the EB patient foundations. We didn’t have enough NIH dollars. And the patients and the families sold cookies, ran marathons, did everything they can (26:49) to ask people to put money in the jar for us. So that can’t be replicated for every patient disease or problem. And that is the role of the government. And I’m sorry to get on my high horse, but we can do better as Americans. 

 

SREENIVASAN: Michael Hund, and Dr. Jean Tang, thank you both for joining us. 

 

HUND: Thank you, Hari.

TANG: Thank you.