Gene therapy extinction of the dominant centronuclear myopathy mutation is still effective one year later in mice

The proof of concept of an early treatment with an siRNA specifically silencing the mutated allele of the DNM2 gene in a mouse model and in human fibroblast-derived cells carrying the most frequent mutation in centronuclear myopathy (p.R465W) was published in 2018 by a team from the Research Centre of the Institute of Myology (Paris)

Efficacy that lasts over time

The team continued its work and published in February 2022, the long-term results of this therapeutic strategy in the same model mouse.

One year after a single injection of an AAV-shRNA specific to the mutation :

• restoration of the muscle phenotype is complete
• the decrease in the level of mutated transcripts was maintained.

This strategy was not effective when administered late to 6-month-old model mice, even at doses ten times higher.

 

Benefits of therapy by dynamin-2-mutant-specific silencing are maintained with time in a mouse model of dominant centronuclear myopathy. Trochet D, Prudhon B, Mekzine L, Lemaitre M, Beuvin M, Julien L, Benkhelifa-Ziyyat S, Bui MT, Romero N, Bitoun M. Mol Ther Nucleic Acids. 2022 Feb 13;27:1179-1190.