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.