Enhancing AAV9-UFμDys1 Gene Therapy Efficacy Through Immunosuppression in Mice with Pre-Existing Immunity and Enabling Redosing Strategies for Duchenne Muscular Dystrophy

https://www.liebertpub.com/doi/10.1177/10430342251385586?utm_campaign=MAL_HUM&utm_medium=email&_hsenc=p2ANqtz--Gkfnchb5GKygccXAOAN-ACNiRwdUHl8xco1_dsMrrwxXwHVV-vDMJ53c37HXHRXCdbqyD5Ljo5iDJr4j6px8rw0b67w&_hsmi=388578002&utm_content=388578002&utm_source=hs_email New Rochelle, NY, November 10, 2025—A new study in the peer-reviewed journal Human Gene Therapy describes an immunosuppression strategy aimed at mitigating detrimental immune responses to the adeno-associated virus (AAV) capsid that delivers gene therapy to patients with Duchenne Muscular Dystrophy (DMD), while enhancing microdystrophin expression. Click here to read the article now. Barry Byrne, MD, PhD, from the University of Florida, and coauthors, used an optimized AAV9 expression cassette to achieve sustained microdystrophin expression in the heart and striated muscles in mice. The investigators observed a 40% improvement compared to the animals that received a control AAV9 vector. Delivery of the optimized AAV9 vector in combination with a single-dose immunosuppression strategy effectively reduced total anti-AAV antibody levels and increased microdystrophhin expression in treated mice. This strategy enabled repeated AAV administration and expanded the therapeutic window for DMD gene therapy. “In the present study, we created a new microdystrophin (UFμDys1) and tested the ability of a combination IMS therapy with clinically approved and safe immunosuppressive drugs,” stated the investigators. “Here, we demonstrate that repeat administration of a divided AAV dose along with combination of IMS can increase the expression of the transgene, compared to a single cumulative dose AAV vector or the absence of IMS. Furthermore, our data supports that the combination IMS regimen can successfully reduce the total antibody titer against AAV in the setting of pre-existing. Immunity and permit transgene expression after systemic AAV delivery.” “It is very exciting to see advancements like this progressing gene therapies towards clinical use for patients. This is a very promising strategy to increase the effectiveness of AAV-based therapies for DMD patients and could be applied to treatment strategies for other genetic diseases,” says Managing Editor of Human Gene Therapy Thomas Gallagher, PhD, from the University of Massachusetts Chan Medical School.