NIH Strategizes to Streamline Gene Therapy Development

PJ Brooks, PhD

Credit: Washington University in St. Louis

The development of novel therapies for underserved populations with rare diseases faces many challenges, including rarity, biotech support, clinical trial recruitment, and heterogeneity. The National Institutes of Health (NIH) has several initiatives it is pursuing to help facilitate rare disease drug development.

CGTLive^® spoke with PJ Brooks, PhD, deputy director, Division of Rare Diseases Research Innovation, National Center for Advancing Translational Science (NCATS), NIH, to learn more about the work the NIH is doing and some focuses the organization plans to target in the near future. Some programs include the platform vector gene therapies project and the Bespoke Gene Therapy Consortium (BGTC) that aims to develop a platform that can produce bespoke gene therapies for rare diseases.

How is the NIH working to streamline gene therapy development for rare diseases?

PJ Brooks, PhD: The platform vector gene therapies project is focused on how we can use the fact that we use the same AAV serotype as a platform for more than one disease, and how that can potentially streamline the regulatory process, which is the main focus of that effort. The BGTC is a public private partnership organized by the Foundation for the NIH, which is not actually part of the NIH. That is an important point because that allows us to work with private industry in ways that we couldn't otherwise and share insights in a pretty competitive space. Within the BGTC, we're really trying to focus on streamlining navigation of the regulatory path. But to do that we're developing AAV gene therapies for a total of 8 diseases. But all of those diseases are so rare that there is no commercial interest. And that means that almost by definition, we're in the pre competitive space. And that is really valuable in terms of people sharing insights. And I also mentioned that a really important part of that program is part of the vision of Peter Marks, director of the Center for Biologics at FDA, because I think his enthusiasm for that was really essential to get this program up and running. So those are both along the lines of what we're trying to do to streamline the path to AAV gene therapies.

Can you talk about the genome editing program you’re involved with?

Brooks: The somatic cell genome editing program that I'm involved with at the NIH was funded by the NIH Common Fund, part of the Office of the Director. We're really focusing there on how we can develop gene editing as a therapeutic platform. And in particular, the idea that you can have one editor and one delivery system. Once that is shown to be safe in a patient with one mutation, you could then extend that to additional mutations or possibly even additional diseases in a more streamlined fashion, because the key parts of that treatment, the editing and the delivery system, would have, in principle, been shown to be safe. And that idea would, I think, be a very nice therapeutic platform, and in my view, might be the most efficient way to get to more than one disease without having to go through an individual drug development pathway for each individual disease, or even into each individual mutation, which is just clearly not going to work. So, I think there's a lot of excitement there. And a lot of the things we're funding are trying to test out that pathway and see how the FDA reacts to it. A big focus of all of this is really doing work to interact with the regulatory agency, but then make those learnings available to the broader community. That is something that the FDA cannot do by law, and most private companies would not do because they would be giving away their intellectual property.

With the genome editing program, we're specifically funding people not just to do clinical trials and get ready for clinical trials, we’re actually funding them to think about new ways to do these clinical trials with genome editing faster and more efficiently, and to go propose and discuss these things with the FDA. And then we're going to disseminate that. So, I think it's a bit of a different approach to funding research than we've done. But I think it's very timely, because the field is shifting, and it's based on emerging science. The FDA is developing their regulatory pathways based on the emerging science, some of which NIH is funding. And I think that through this process, we're getting some really valuable insights that can, I think, benefit the whole field. So that's something I'm excited about. And more generally, something that, you know, we think a lot about it in NCATS is finding ways to not do things one disease at a time wherever possible. Looking at it now, there’s possibly 10,000 or so rare diseases, and we just can't do them one at a time. And I mean, 80% of them are monogenic, it's the same problem in all of them. The gene is different, the tissue you have to target is different, but the fundamental problem and the fundamental solutions are the same. So, I think that's something that we're we're very excited about.

This content has been edited for clarity.