Drug Repurposing Screening for Two Ultra-Rare Maternally Inherited Mitochondrial Diseases—MELAS and LHON-Plus

Authors

  • D Li
  • M Uittenbogaard
  • A Chiaramello
  • C Chen
  • W Zheng

Abstract

Mitochondrial diseases are a large group of genetically heterogeneous and clinically diverse disorders, including both neurological and non-neurological symptoms. In this project, we focus on two ultra-rare mitochondrial diseases MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes) and LHON-Plus (Leber’s hereditary optic neuropathy-Plus). They are caused by a maternally inherited pathogenic variant that results in a defective oxidative phosphorylation pathway responsible for mitochondrial ATP synthesis. Both diseases share the molecular etiology of Complex I deficiency, causing ATP deficiency and chronic energy deficit. We are using four patient-derived dermal fibroblasts samples, two from MELAS patients (one with the pathogenic mitochondrial variant, m.3243A>G and the other with the m.14453G>A), and two from LHON-Plus patients (one with the m.11778G>A and the other with the m.3460G>AA) to screen the LOPAC and NPC2.1 (approved drugs) libraries. The aim of this study is to identify repurposing drugs that enhances mitochondrial bioenergetics by assessing the mitochondrial membrane potential.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Tuesday, August 6, 2024