Cardiac complications observed in rats treated with microdystrophin

French researchers, in collaboration with the Généthon laboratory, report the results of a study conducted on rats with Duchenne muscular dystrophy (DMD) treated with microdystrophin gene therapy:

• this work comes in the context of toxicity observed in some DMD patients who received microdystrophin using an 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). viral vector;
• a rat optimised to best mimic DMD (DMDmdx) received injections of the transgene at various doses, compared to healthy rats,
• the rats treated with the highest dose experienced a significant number of sudden deaths, possibly related to cardiac arrhythmias.

Although it remains difficult to draw a formal parallel with the therapeutic trials currently underway, the authors stress the need for caution with this type of AAV-mediated gene therapy, especially at high doses.

Dose- and genotype-dependent cardiac arrhythmia and sudden death in rats following microdystrophin gene therapy. Le Guiner C, Toumaniantz G, Larcher T, et al. Mol Ther. 2025 Oct.