A preclinical study evaluated SAR446268, an artificial microRNA produced by an AAV vector and targeting DMPK (dystrophin myotonic protein kinase) RNA designed by Sanofi, in Steinert’s disease or type 1 myotonic dystrophy (DM1).
A single intravenous injection in mice modelling the disease resulted in a decrease in the amount of DMPK RNA in muscle and heart cells, but not in the liver, confirming the muscle specificity of the therapy. An improvement in cardiac output and myotonia was also observed.
When administered to primates, the treatment was well tolerated and induced a dose-dependent decrease in DMPK gene expression (up to 90%) in major muscle groups, including the heart and diaphragm.
These data provide preclinical evidence of efficacy and safety. They justify the launch of the Phase I/II clinical trial, BrAAVe, which is currently recruiting (NCT06844214).
