From Grad Work to Gene Therapy Approval

The research leading to the approval of adeno-associated virus (AAV) vector-based gene therapy products like Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), which is intended to treat Duchenne muscular dystrophy (DMD), has a history stretching back decades. At the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 3-6, in Orlando, Florida, the organization awarded their MDA Legacy Award to Jeffrey Chamberlain, PhD, Professor, Neurology and Medical Genetics, and Adjunct Professor, Biochemistry, and McCaw Endowed Chair of Muscular Dystrophy at University of Washington, for his pioneering work in the field of neuromuscular gene therapy.

At the conference, CGTLive® sat down with Chamberlain to hear about the talk he gave in association with receiving the reward. He went over the history of his work and its relevance to modern gene therapy research programs.

CGTLive: Congratulations on your MDA Legacy Award. Can you tell us a little bit about the talk that you gave with that?

Jeffrey Chamberlain, PhD: It was very exciting for me to be able to receive the MDA Legacy Award this year. It's somewhat of a lifetime achievement award that MDA has started giving out. They asked me in association with the award to give a brief overview of my career, which was a bit challenging because I've been at this for a while. But I just kind of outlined some of the things that I've done that I thought are relevant to current therapeutics. That spans actually all the way back to my graduate work, where we started developing muscle-specific promoters that have turned out to be very useful in gene therapy, which is surprising because we had no idea about gene therapy at the time we were doing that work.

I transitioned from that into molecular genetics and began working on muscular dystrophy. In particular, we focused on a mouse model for muscular dystrophy and did some of the initial characterization of that model. We then began cloning out the mouse gene equivalent to the one that is defective in human DMD. Initially we were planning on doing just structure function studies trying to find out what this protein did and why when it was missing you got this devastating disease. In doing so, we started creating new mouse models and realized we were having a therapeutic impact. That spurred my interest in gene therapy.

The rest of my talk was just kind of summarizing how we went from there to developing different vectors and how we started working with AAV vectors and discovered for the first time that you could use AAV to deliver genes body-wide to the muscles. We combined that with some of our work with the some of the dystrophin clones and developed a couple of vectors that we call microdystrophin vectors. Several of them are now in human clinical trials, one of which was just approved last year as the first gene therapy for DMD. It was very exciting for me to be able to go through that arc from my early graduate career days to having a drug being approved for human use.

This transcript has been edited for clarity.

Click here to view more coverage of the 2024 MDA Conference.

REFERENCE
Muscular Dystrophy Association Announces Recipient of 2024 MDA Legacy Award for Achievement in Research, is Jeffrey Chamberlain, Ph.D., Leading Professor in Gene Therapy. News release. January 30, 2024. https://finance.yahoo.com/news/muscular-dystrophy-association-announces-recipient-145900986.html