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 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.
