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-alpha). 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-alpha, 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-alpha inhibitors may be necessary to truly alter and/or reverse the deleterious effects of this form of muscular dystrophy.
Lefkowitz
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Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa, FL 33612, USA. slefkowi@tampabay.rr.com
Lefkowitz
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D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004110:Diltiazem / Q000627:therapeutic use*; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D033741:Adenine Nucleotide Translocator 1; D014409:Tumor Necrosis Factor-alpha; D004110:Diltiazem; D002118:Calcium