Barry J Byrne, MD, PhD, on Overcoming the Hurdles Presented by Immunity to AAV Vectors


The chief medical advisor of the Muscular Dystrophy Association discussed research he is working on with the goal of increasing eligibility for gene therapies and opening the door to redosing.

“One of the things that we've been investigating with the support of the Muscular Dystrophy Association is how to sustain the effect of what are transformative therapies, particularly in Duchenne muscular dystrophy. That involves mechanisms to minimize immune response and improve safety of gene therapy products, as well as the potential to top off the effects or potentially make accessible for patients new therapies when they become available.”

Many gene therapy products that have received approval for use in the United States, as well as an even greater number that are currently being evaluated in preclinical or clinical studies, utilize adeno-associated virus (AAV) vectors to deliver a strand of DNA encoding a gene of interest for treatment. Although AAV vector-based approaches have enabled the delivery of transformative treatments to patients with a range of diseases, the method is imperfect. One of the issues presented by AAV vector-based gene therapies is that some patients have natural immunity to the vector because of previous environmental exposure to AAVs or similar viruses. As such, their body seeks to destroy the AAV vector delivering the gene therapy, hindering efficacy and presenting a potential safety risk. Furthermore, patients who are able to receive treatment with gene therapy successfully may also develop immunity to AAV vectors as a result, which closes the door on potential future redosing with the same gene therapy or dosing with other AAV vector-based gene therapies in the future. Although some researchers are seeking alternative delivery methods to AAV vectors for gene therapies in order to solve these problems, some are focused on finding new means of addressing the immunity issues to AAV directly.

Barry J Byrne, MD, PhD, the chief medical advisor of Muscular Dystrophy Association (MDA) and a physician-scientist at the University of Florida, and his colleagues are currently investigating the latter approach with funding from the MDA. As part of a larger discussion about the MDA’s activities and the upcoming Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, which will be held on March 3-6, 2024, in Orlando, Florida, CGTLive™ asked Byrne about his research. He noted that they are exploring the potential use of efgartigimod alfa (marketed as Vyvgart), a drug originally intended to treat myasthenia gravis, to lower AAV antibody levels.

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