METHODS FOR THE TREATMENT OF MITOCHONDRIAL GENETIC DISEASES

摘要

The invention relates to a method for treating mitochondrial genetic diseases. The inventors have worked with primary fibroblasts from patients and control individuals and collected protein lysates for western blotting. Importantly, they observed that the genetic mitochondrial disorders, show a significant increase in phosphorylation of ribosomal protein S6 (pS6) compared to control fibroblasts, indicative of hyperactivated mTOR signaling. Patients with mitochondrial disorders and controls cells were treated for 48 hours with DMSO or BYL719. All lines from patients with mitochondrial diseases show reduced membrane potential, determined by TMRE staining intensity, and abnormal morphology, fragmentation and the presence of depolarized (low TMRE staining) mitochondria. Treatment with BYL719 attenuated these phenotypes in all MELAS fibroblasts while having no overt impact on the control cells. Similar experiments using flow cytometry confirmed membrane potential (TMRE) rescue by BYL719 treatment in MELAS fibroblasts.