Following the serious side effects observed during trials of micro–dystrophin gene therapy using an AAV viral vector in Duchenne muscular dystrophy (DMD), researchers at the Institute of Myology undertook to investigate the mechanismsinvolved in greater depth:
- a transgenic mouse with a double knockout for dystrophin and utrophin was used as an experimental model,
- treated with micro-dystrophin using an AAV delivered systemically, this mouse showed a significant prolongation of survival and improved cardiac function, at least during the first twelve months post-injection,
- however, additional histological analyses revealed thickening of the cardiac septum and, above all, a significant degree of inflammation with the presence of related biomarkers.
These findings are highly relevant in the context of the few cases of medium- to long-term myocarditis observed in some DMD patients who participated in clinical gene therapy protocols.
