Innovations in Gene Therapy for Rare Disease Treatment with Dr. Jerry Vockley

Released: 10/4/2022

In this episode of That’s Pediatrics, our hosts talk with Jerry Vockley, MD, PhD, director of the Center for Rare Disease Therapy (CRDT) and chief of Medical Genetics Division at UPMC Children’s Hospital of Pittsburgh.

In this episode our experts discuss:

  • What gene therapy is (1:19)
  • The actual prevalence of rare diseases (3:04)
  • All about Fatty Acid Oxidation Disorders (4:45)
  • How the internet helps patients with rare disorders connect with treatment (8:01)
  • The unique role of the CRDT at UPMC Children’s (10:15)
  • Educating patients regularly through the CRDT Webinar Series (11:07)
  • The Gene Therapy Symposium on November 3, 2022 in Pittsburgh (11:35)
  • Why gene therapy is the future (12:51)
  • Who the Gene Therapy Symposium is for (14:48)
  • What Dr. Vockley sees in the next five years for gene therapy (17:34)

Meet Our Guest

Jerry Vockley, MD, PhDGerard (Jerry) Vockley, MD, PhD, is a medical geneticist and is certified in clinical genetics and biochemical and molecular genetics by the American Board of Medical Genetics and Genomics. He is chief of the Division of Medical Genetics and director of the Center for Rare Disease Therapy at UPMC Children’s Hospital of Pittsburgh and is the Cleveland Family Endowed Professor of pediatric research at the University of Pittsburgh School of Medicine. He received his medical degree and doctorate degree from the University of Pennsylvania and completed his residency at the University of Colorado, followed by his fellowship at Yale University School of Medicine. Dr. Vockley’s clinical interests include inborn errors of metabolism including organic acidemias, phenylketonuria, maple syrup urine disease, fatty acid oxidation disorders, and mitochondrial respiratory chain deficiencies. He has published over 280 articles on multiple clinical and research topics. He is a member of the Board of the American College of Genetics and Genomics and is an active member of the Society for Inherited Metabolic Disorders, the American Society of Human Genetics, the Society for the Study of Inherited Metabolic Diseases, and the American Society of Clinical Investigation.

Meet Our Hosts

Allison WilliamsAllison “Alli” Williams, MD, is a pediatric hospitalist and is certified by the American Board of Pediatrics. She is a member of the Paul C. Gaffney Division of Pediatric Hospitalist Medicine, medical-surgical co-management team director, and assistant professor at the University of Pittsburgh School of Medicine. Dr. Williams received her medical degree from Herbert Wertheim College of Medicine at Florida International University in Miami, Florida, and completed her residency at UPMC Children’s Hospital of Pittsburgh. Her clinical interests include non-RSV bronchiolitis, febrile neonates, and the enhanced of patient care through medical-surgical co-management.

Sameer AgnihotriSameer Agnihotri, PhD, is director of the Brain Tumor Biology and Therapy Lab and an assistant professor at the University of Pittsburgh School of Medicine. Dr. Agnihotri earned his bachelor’s degree in biology, specializing in genetics, followed by his doctorate degree in medical biophysics, both at the University of Toronto. While there, he used genetic screens to identify novel drivers of glioblastoma, an incurable brain tumor. He subsequently completed his post-doctoral fellowship at the Arthur and Sonia Labatt Brain Tumor Research Centre at the Hospital for Sick Children, in Toronto, and the Princess Margaret Cancer Centre, Division of Neuro-oncology Research, also in Toronto. Dr. Agnihotri’s lab studies pediatric and adult high-grade gliomas.


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Voiceover: This podcast is for informational and educational purposes only. It is not medical care or advice. Clinicians should rely on their own medical judgements when advising their patients. Patients in need of medical care should consult their personal care provider. Welcome to "That's Pediatrics", where we sit down with physicians, scientists, and experts to discuss the latest discoveries and innovations in pediatric healthcare.

Dr. Alli Williams: Welcome to That's Pediatrics. I'm Alli Williams, a pediatric hospitalist here at UPMC Children's Hospital of Pittsburgh.

Dr. Sameer Agnihotri: I'm Sameer Agnihotri. I'm a scientist in the Department of Neurological Surgery. It's an absolute honor to have Dr. Jerry Vockley here. To say that he's a pioneer, an all star, a superstar, we'd be here for multiple hours. So it's an honor to have you. You are the division director of Genetic and Genomic Medicine. We'll have all your other titles, but it's just an absolute pleasure to have you here. And I think we want to lead off with a very broad question. What is gene therapy?

Dr. Jerry Vockley: Oh, well, gene therapy. Thank you for that introduction, by the way. It's a good thing it's a podcast, they can't see me roll my eyes. Gene therapy, in a very unscientific definition, is the holy grail of genetic treatment. If you have a genetic disease, that is a disorder caused by a mistake in one of your genes, what better way to fix it or to treat that disease than by actually fixing the gene or giving you a new one? And that really in the broadest sense of the term is what gene therapy is. It has a lot of different manifestations. People may have heard about gene editing. That's a technique where you can actually go in figuratively, of course, and edit the gene in the cell, change the gene, and fix the mistake. And so now the individual literally doesn't have that disease anymore.

Dr. Williams: Wow.

Dr. Vockley: The other broad category of gene therapy in the context of genetic disease and rare disease is the gene replacement or augmentation. So instead of trying to figure out how to fix the gene that's there, let's just give you a new copy of it. And technically that's a lot easier it turns out, but both are currently in development. And in fact, in clinical trials right now, including here at Children's.

Dr. Williams: This must be so difficult to treat and to study as most of these syndromes and diagnoses that you're working on this with are so rare.

Dr. Vockley: They are. The statistics are interesting because if you look at any of these disorders, most of them, the most common of them may occur actually one in a few thousand individuals. So fairly common, but the rarest of them may be one in a million. However, there's 7,000 of them. So you add them all up. And it turns out that 2 to 3% of all babies born, U.S., worldwide, have a genetic condition, something that requires that they seek medical attention. And so, although individually, they're rare. In aggregate, they're common. But the aggregation doesn't make the difficulty or change the difficulty because everyone has to be treated differently. So it is a different therapy for every genetic disorder.

Dr. Agnihotri: Can you share with us in your amazing career, the amazing research you've done, something that you're really passionate about and what your lab is focusing on?

Dr. Vockley: Oh my gosh. How long do we have for the podcast? I'm excited about everything. Can you tell?

Dr. Agnihotri: Right. Whatever you're willing to share. You've got so much, but it'd be nice to like-

Dr. Vockley: Well, I'll tell you what. Tomorrow, we are hosting the family support group in their annual meeting of families who are with individuals with disorders of fatty acid oxidation. That's a set of disorders where the defect is involved with the cell's ability to make energy. When you are fasting, when you are under stress, when you're sick, or when you're trying to run a marathon, your body doesn't have enough energy to do that with its usual stores, which is the glucose that's floating around in the blood. You burn that up very, very quickly, within a couple of hours. And so the body has built in alternatives to that, but they take a while to kick in. And the sort of ultimate level of that is fatty acid oxidation.

It's what you're trying to do when you lose weight. You want to burn that fat that your body is stored and then take it and use it for fuel. Well, that requires about two dozen different enzymes, each of which is encoded by a gene. And it's such a new group of disorders that I've actually been in clinical practice for the definition of all of them, and have been part of defining them as well. So it's one of the things that I'm particularly proud of. But for so long, genetics has been a diagnostic specialty. We've been the diagnosticians of last resort. Nobody knows what's going on. Okay, let's send them to genetics. And then we wave our magic wand and can come up with an answer.

And the most exciting part about genetics right now is that we're transitioning to being a therapeutic specialty. And so with fatty acid oxidation disorders, I was responsible for developing, and it has now been approved, the first medication to treat long chain fatty acid oxidation disorders.

Dr. Williams: Wow.

Dr. Vockley: Was approved a couple years ago. And it's really been life altering for most families. It's not a cure. It's not gene therapy, although we're working on that too, but it cuts hospitalizations in half, and it cuts hospital stays in half. And in particular, it treats the life threatening symptoms of fatty oxidation disorders in a way that has cut mortality. Well, never say zero, but when 70% of these kids used to die by the age of 10 or 15, and now it's actually rare for that to happen. So it's a big change and gives us time to work on these other disorders, these other kinds of therapies.

Dr. Agnihotri: Right.

Dr. Williams: That's astounding. How do you get the word out about this then? I mean, you're changing from not only diagnosis to treatment. How do you share this information with these families when they're few and far between?

Dr. Vockley: They find us. One of my favorite reasons for referrals, I found you on the internet. The internet's an amazing resource to families with rare disorders. And so, I mean, if you Google fatty acid oxidation disorder, chances are probably the first couple of dozen hits you'll get will be me. It's just because I've been doing this for such a long time.

But then the groups, like I mentioned earlier are also very, very active and they all have social media outreaches. I hate to say podcasts, notwithstanding. I'm a bit of a social media Luddite. I do have email, but I don't tweet and I don't dance and any of those other things. So the families are in constant communication. So they really are one of the best ways to get information out. I'll talk to them through the weekend and that word will get out there and of course it'll all be recorded. So other folks will be able to see it online. And it'll be streaming as well so people will be online live.

Dr. Agnihotri: There's so much excitement in this field right now. Can you tell us a little bit about upcoming symposiums and events that people in the field should be keeping an eye out for?

Dr. Vockley: Yes. Well, there are tons of them, but of course, we're going to talk about mine.

Dr. Agnihotri: Right.

Dr. Vockley: So one of the titles that you did mention is I started and direct a program here at Children's called the Center for Rare Disease Therapy. And when we were starting it, I used to have my faculty would say, "Well, how's that different than genetics? Isn't that what we always already do?" And I said, "Yeah, yeah, yeah. But we have all these other disciplines that we work with, and these are complicated patients. And really, we work better as a team." And so the CRDT was established really to try to make sure that we were able to assemble the right teams for the right diseases as one component of what we do.

And another major component of what we do is try to make those services available nationally. So we have concierge opportunities for families to call in and say, "I need to come somewhere where they know what I've got." Excuse me. And then we help them navigate the system here. But the other big thing that we do, and this comes back to the question about symposia, is education. So we have an ongoing webinar series once a month or thereabouts. We do a webinar. It's streamed live and recorded. So those are available on the CHP, or will be soon. I think we're moving them to the CHP YouTube channel. I think I said that right.

And this fall, what we are going to be doing, this will go out... I guess, it's still fall. November 30th we're going to be hosting a symposium on gene therapy. That's going to be a way of, we hope, introducing our local community for sure. It'll be recorded and available for streaming to gene therapy because one of the main things that’s going to change the future in rare diseases is gene therapy. And so as part of what's going on here at Children's now, we have, it's at least a dozen different gene therapy clinical trials going on right now. And we are giving one clinically approved gene therapy on a regular basis. And so my assumption, and I've been fortunate to be able to convince much of the hospital of this, the powers that be, that gene therapy's really the future. And that we need to be able to embrace the experience that we have in gene therapy on a research basis, and translate that over into clinical practice as these therapies become approved by the FDA.

In the early going, there aren't going to be a lot of places that are comfortable doing gene therapy. And so folks are going to be left with the conundrum of finding someone who can deliver a therapy that they just heard about. They've got this brand new thing that now they can fix their child or themselves, but of course their local hospital doesn't do it. And maybe even their local tertiary care medical center doesn't do it. So they're going to Google, and they're going to find the Children's Hospital of Pittsburgh gene therapy program. So it's a really exciting opportunity.

And the symposium this fall will feature some of our own faculty who are involved in gene therapy research and clinical trials. We'll also be bringing in two really outstanding international experts who have developed gene therapies that are now in clinical trials. And so it'll just be an opportunity for anyone who can come to Pittsburgh, and you're certainly welcome to come in person, to come and be part of that. Talk to the experts, have lunch, very, very informal, but also get a half a dozen really top notch lectures that will be on the cutting edge of gene therapy.

Dr. Williams: And who's the symposia targeted towards? Is it towards pediatricians? Is it towards the patients? Who should come to this?

Dr. Vockley: Well, the knowledge gap between patients and PCPs is narrowing in the rare diseases. Sometimes the PCPs call me up and say, "My family's telling me about this new therapy. What all do I need to know?"

Dr. Williams: Exactly.

Dr. Vockley: So the answer is a little bit of both. We're specifically targeting to care providers. So we're hoping our internal folks will be interested in coming to it, the hospital staff and physicians. But we also hope that we'll get some interest from our community pediatricians or anybody who out there who might be interested in coming. However, I do think that a motivated family member or patient who wants to come and hear some of this first hand would not walk away disappointed.

Dr. Williams: That's excellent. And you said it was going to be in person if you're able to come to Pittsburgh. It's also going to be recorded. Is it going to be live streamed?

Dr. Vockley: It's going to be recorded. We don't think it's going to be live streamed simply because that ends up being a lot more complicated. But I don't know. If your vast audience starts start sending in emails and flooding you saying, "What do you mean it's not going to be live?" Well, we could make it work. So you tell me.

Dr. Williams: And how do we find the symposium to register for it? When does registration open?

Dr. Vockley: We don't have it up yet, but it should be soon. Google is your friend. And so keep tabs, or if you just Google Children's Hospital of Pittsburgh CRDT, you'll get to our webpage. And it's going to be, if not already it will soon be up there on the landing page, the homepage. And you'll be able to get to it. Our registration is going to be minimal. I think we talked about something like $100 and if there's somebody out there who's choking on that and saying you can't afford it, don't worry about it. Just send us an email and we'll make sure you get into the program.

Dr. Agnihotri: Yeah, this is absolutely fantastic. So when I was an undergrad learning about gene therapy, it was science fiction. And now in my lifetime, I'm seeing it get into clinical trials. From your perspective, you've seen it all transitioning from diagnostics to therapeutics. What do you see for the next five years? Because it's just absolutely amazing what we can do now.

Dr. Vockley: Well, so gene therapy's been just around the corner for the last 30 years.

Dr. Agnihotri: Right.

Dr. Vockley: And so I hesitate to prognosticate, but it is fair to say that gene therapy isn't around the corner, it's here.

Dr. Agnihotri: Right.

Dr. Vockley: And so in the next five years, if you just look at the number of clinical trials that are out there now and follow the natural course of those efforts, it is quite likely that in the next five years we'll probably have a couple of dozen approved therapies. And in the next 10 years, that's going to be closer to somewhere between 50 and 100.

The challenge here is that when you've got 7,000 diseases, each of which you have to develop one at a time, and it takes tens of millions of dollars to do and five years, is there's a critical bottleneck there that the system and the FDA just have not yet fundamentally addressed. There are ways to be able to try to speed up the process, but it makes a lot of people who do traditional drug development uncomfortable, because it feels like a shortcut. And in fact, what we're saying is we will never shortcut safety. We will never shortcut proving efficacy, but there are ways of batching development, or at least certain stages of development, that can ultimately make the development of any one therapy a lot less expensive and therefore more available. And then speed it up, both of which will also impact the amount of money necessary to develop one of these therapies.

Dr. Agnihotri: And for fellow clinicians and researchers on your webpage, can we get some of the reviews that you've written and other primary works in terms of gene therapies, just as a primer?

Dr. Vockley: Remember what I said about being a social media Luddite?

Dr. Agnihotri: Yeah.

Dr. Vockley: I'm pretty sure I have a webpage out there.

Dr. Agnihotri: Right. You got one.

Dr. Vockley: The department has made sure of that. And I'm pretty sure you can link to all my publications from there.

Dr. Agnihotri: Right.

Dr. Vockley: Many of which are available through the NCBI, the National Center for something something. Anyway, it's where all the papers live and many of them are up there free for access. And there are also links to some of this stuff on the CRDT webpage, though, I have to admit, because a lot of that requires some user involvement, meaning me, it has a tendency to lag a little bit.

Dr. Agnihotri: Right.

Dr. Williams: Well, so what I heard you say is that gene therapy is not only the future, it is here now. And there's a symposium to talk about it coming up at the end of November, which is very exciting. So if you go to the Children's main page and you look up the Center for rare Diseases, you should be able to get to that. We'll also make sure that on this podcast we have links to it so that you're able to find that. Worse comes to worst, just Google Dr. Vockley and I'm sure you'll get there eventually, too. So thank you so much again for coming today and talking with us about this. This was very exciting, and we look forward to hearing about the success of your symposium.

Dr. Vockley: My pleasure. Was great to talk to you. Thanks for the time.

Dr. Williams: Thank you.

Dr. Agnihotri: Thank you.

Dr. Vockley: Bye-bye.

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This podcast is for informational and educational purposes only. It is not medical care or advice. Clinicians should rely on their own medical judgements when advising their patients. Patients in need of medical care should consult their personal care provider.