Metformin rescues muscle function in BAG3 myofibrillar myopathy models.

Dominant mutations in the co-chaperone BAG3 cause a severe form of myofibrillar myopathy, exhibiting progressive muscle weakness, muscle structural failure, and protein aggregation. To elucidate the mechanism of disease in, and identify therapies for, BAG3 myofibrillar myopathy, we generated two zebrafish models, one conditionally expressing BAG3 and one with a nonsense mutation in . While transgenic BAG3-expressing fish display protein aggregation, modeling the early phase of the disease, fish exhibit exercise dependent fiber disintegration, and reduced swimming activity, consistent with later stages of the disease.