A first step towards the possibility of administering gene therapy in subjects already immune to AAV

American researchers in Indiana have studied ways to overcome the obstacle posed by the presence of neutralising antibodies in patients who need to undergo viral vector-mediated gene therapy:

• to this end, an optimised Duchenne muscular dystrophy (DMD) transgene was inserted into an AAV9 (AAV9-UFµDys1), and the injection was performed on mdx mice models of DMD, preceded by an immunosuppression protocol developed by the researchers.
• Thanks to this protocol, the treated mice saw their cardiac and muscular functions improve by 40% compared to untreated mice.
• Furthermore, the mice treated after the immunosuppression protocol saw a significant increase in dystrophin expression in the heart and muscles compared to mice treated without the prior protocol.
• It should be noted that the mice had been previously immunised against AAV« adeno-associated virus » , ou virus adéno-associé est un petit virus à ADN simple brin. Il fait partie de la famille des Parvoviridae et appartient au genre des Dependovirus. La particule virale est constituée d’un brin d’ADN de polarité positive ou négative protégé par une capside. La taille moyenne d’une particule d’AAV et de 18 à 22 nm. Les AAV sont les seuls parvovirus non autonomes. Lorsqu’on emploie « rAAV » , il s’agit du virus AAV recombinant, c’est-à-dire qu’il a été modifié pour devenir un vecteur (et n’est donc plus virulent). to recreate the experimental conditions in human clinical trials.

This work is currently limited to animals, but could quickly lead to interesting developments in humans, provided that the necessary immunosuppression is well tolerated.

Enhancing AAV9-UFμDys1 Gene Therapy Efficacy Through Immunosuppression in Mice with Pre-Existing Immunity and Enabling Redosing Strategies for Duchenne Muscular Dystrophy. Saha M, Bhake R, Meyers CA, et al. Hum Gene Ther. 2025 Oct