Fascioscapulohumeral muscular dystrophy: A progressive degenerative disease that responds to diltiazem

The authors believe that with fascioscapulohumeral muscular dystrophy (FSHD), like Duchenne muscular dystrophy, there is Ca2+ dysregulation in the muscle cells. The dysregulated Ca2+ can cause cell death in various ways. One mechanism may be Ca2+ triggering abnormal levels of tumor necrosis factor (TNF-α). Another mechanism may involve excessive Ca2+ levels within the mitochondria which would cause this organelle's membrane to collapse ultimately inducing apoptosis and/or necrosis. With this in mind, it has been reported that in FSHD there is over expression of adenine nucleotide translocator-1 (ANT-1). This Ca2+ dependent protein, which is a component of the mitochondrial permeability transition pore, could be an important culprit in mitochondrial membrane collapse. Therefore, dysregulated Ca2+ as well as TNF-α, in addition to over-expression of ANT-1, may result in cell disruption ultimately causing the characteristic dystrophic muscle wasting. The present investigators have noted that some individuals with FSHD benefit from a regimen of diltiazem, a Ca2+ channel blocker. Initial results using diltiazem may represent the first beneficial treatment for a form of muscular dystrophy. Even if there is only a slowing of progression, this would be a positive first step. A combination of several different Ca2+ regulating agents and TNF-α inhibitors may be necessary to truly alter and/or reverse the deleterious effects of this form of muscular dystrophy.