A recent review study suggested that combination therapies may be the most optimal pathway to treat myotonic dystrophy. A few years ago when the defective pathway for myotonic dystrophy was identified it was proposed that treatment would be easy to find as it was proposed that the clumping would be easy to defeat. This has proven not to be the case. Here is a summary from the study:
One potential strategy is a combination approach (e.g., dierent small molecule
combinations, small molecules plus ASOs, transcription inhibition plus RAN protein ablation, etc.)targeting multiple processes and allowing synergy in disease modulation. As proof of concept, a recent study reported that two previously characterized compounds that separately displayed ecacyin DM1 models, furamidine and erythromycin, displayed an even greater rescue of mis-splicing in
combination than expected from a mere additive eect . Importantly, this combination treatment yielded lower toxicity and fewer o-target eects than when either drug was administered alone inDM1 patient and mouse models . Hence, if combination treatments are a viable therapeutic strategy for treating DM, there are already many unexplored therapeutic avenues that could potentially hold promise. Given the number of small molecule therapies for DM on the horizon, it will be exciting
to follow their development. These studies will lay the groundwork for the eventual therapies for treating DM and will likely illuminate disease biology and treatment avenues for other microsatellite expansion disorders involving toxic RNA mechanisms.