Rapamycin: an adjunctive treatment for post-gene therapy hepatotoxicity with AAV?

American specialists in gene therapy using adeno-associated viruses (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).) have investigated the serious cases of liver toxicity that occurred during gene therapy with microdystrophin (delandistrogene moxeparvovec, Elevidys®) in patients with Duchenne muscular dystrophy:

• four patients treated with this product who developed serious liver damage on average one month after injection were given higher doses of corticosteroids as well as oral rapamycin (sirolimus);
• thanks to this enhanced immunosuppression protocol, the patients, one of whom was already in a wheelchair, regained normal liver function after two months.

This molecule, which is already used for other indications, could soon be included in the recommendations for this condition.

Sirolimus for the treatment of steroid-refractory hepatotoxicity following AAV gene therapy in patients with Duchenne muscular dystrophy. Leon-Astudillo C, Salabarria SM, Chadwick CB et al. J Neuromuscul Dis. 2026 Mar 19:22143602261424971.