A collaboration involving I-Stem, Genethon and the Institute of Myology carried out a high-throughput screening of 2,239 drugs already approved for other diseases and other bioactive compounds on immortalised myoblast models of limb-girdle muscular dystrophy type R2 (LGMD R2) carrying the L1341P missense mutation in the DYSF gene or in muscle fibres from dysferlin-deficient mice:
- only two compounds, bazedoxifene and saracatinib, significantly improved cell survival and strengthened sarcolemma resistance after hypo-osmotic shock.
- saracatinib is thought to act specifically on the folding of the L1341P mutated dysferlin protein, while bazedoxifene exerts a protective effect by stimulating autophagy, including in cells carrying other mutations in the DYSF gene.
These two drug candidates could be potential treatments for LGMD R2: saracatinib specifically targets the L1341P mutation, while bazedoxifene could be effective independently of mutations in the DYSF gene. These preliminary results have yet to be confirmed.
