Valproic acid is protective in cellular and worm models of oculopharyngeal muscular dystrophy.

OBJECTIVE

To explore valproic acid (VPA) as a potentially beneficial drug in cellular and worm models of oculopharyngeal muscular dystrophy (OPMD).

METHODS

Using a combination of live cell imaging and biochemical measures, we evaluated the potential protective effect of VPA in a stable C2C12 muscle cell model of OPMD, in lymphoblastoid cell lines derived from patients with OPMD and in a transgenic Caenorhabditis elegans OPMD model expressing human mutant PABPN1.

RESULTS

We demonstrated that VPA protects against the toxicity of mutant PABPN1. Of note, we found that VPA confers its long-term protective effects on C2C12 cell survival, proliferation, and differentiation by increasing the acetylated level of histones. Furthermore, VPA enhances the level of histone acetylation in lymphoblastoid cell lines derived from patients with OPMD. Moreover, treatment of nematodes with moderate concentrations of VPA significantly improved the motility of the PABPN-13 Alanines worms.

CONCLUSIONS

Our results suggest that VPA helps to counteract OPMD-related phenotypes in the cellular and C elegans disease models.