RYR1-related congenital multi-minicore myopathy: proof of concept in mice for a pharmacological treatment targeting epigenetic changes

A Swiss team has created a mouse model of RYR1-related congenital multi-minicore myopathy with a heterozygous mutation of RYR1 that is isogenic to the one that causes a severe form of congenital multi-minicore myopathy in humans.

Treatment of these mice, which have many features of the human disease, with two molecules targeting DNA methylases (decitabine) and class II histone deacetylases (TMP29), improves the strength of the mice, the amount of RyR1 and the ultrastructure of the muscle (partial restoration of the calcium Ca++ release units or CRUs, and the mitochondria).


Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors. Ruiz A, Benucci S, Duthaler U, Bachmann C, Franchini M, Noreen F, Pietrangelo L, Protasi F, Treves S, Zorzato F. Elife. 2022 Mar 3;11:e73718.