Leveraging High Throughput Screening Methods to Combat Mitochondrial Myopathies in the Context of Complex IV Deficiency
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Mitochondrial disease encompasses a group of genetically inherited disorders characterized by respiratory chain deficiency. These disorders affect 1 in 5000 individuals which translates to approximately 70,000 Americans living with some form of mitochondrial disease. Currently, no cure or effective treatment exists. Tissues that harbor high energy demand such as skeletal muscle tend to be predominantly affected. Patients with mitochondrial myopathies tend to have diminished motor function, painful involuntary muscle spasms, hypotonia etc. Current therapies for mitochondrial myopathies include exercise for those who can tolerate it, vitamins and cofactor treatment etc. However, these treatments have limited impact on disease progression and are more targeted to symptoms. Here, I present a novel approach towards treatment of mitochondrial myopathies which is centered on boosting the regenerative capacity of the stem cells of the tissue to facilitate repair and reduce disease burden. The protein hydrolysate peptone was identified from a small molecule screen as a therapeutic harboring this potential. I show that this compound significantly increased the proliferative capacity of complex IV deficient murine myoblasts by improving cellular energetic pathways and improve the ability of these myoblasts to form myotubes. Peptone mediated rescue of CIV deficient myoblast proliferation also extended to cyanide inhibited human primary myoblasts, pointing to the potential efficacy of peptone as a therapeutic option for human mitochondrial myopathies.