Therapies for mitochondrial diseases and current clinical trials

Mol Genet Metab. 2017 Nov;122(3):1-9. doi: 10.1016/j.ymgme.2017.09.009. Epub 2017 Sep 18.


Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders that result from dysfunction of the mitochondrial oxidative phosphorylation due to molecular defects in genes encoding mitochondrial proteins. Despite the advances in molecular and biochemical methodologies leading to better understanding of the etiology and mechanism of these diseases, there are still no satisfactory therapies available for mitochondrial disorders. Treatment for mitochondrial diseases remains largely symptomatic and does not significantly alter the course of the disease. Based on limited number of clinical trials, several agents aiming at enhancing mitochondrial function or treating the consequences of mitochondrial dysfunction have been used. Several agents are currently being evaluated for mitochondrial diseases. Therapeutic strategies for mitochondrial diseases include the use of agents enhancing electron transfer chain function (coenzyme Q10, idebenone, riboflavin, dichloroacetate, and thiamine), agents acting as energy buffer (creatine), antioxidants (vitamin C, vitamin E, lipoic acid, cysteine donors, and EPI-743), amino acids restoring nitric oxide production (arginine and citrulline), cardiolipin protector (elamipretide), agents enhancing mitochondrial biogenesis (bezafibrate, epicatechin, and RTA 408), nucleotide bypass therapy, liver transplantation, and gene therapy. Although, there is a lack of curative therapies for mitochondrial disorders at the current time, the increased number of clinical research evaluating agents that target different aspects of mitochondrial dysfunction is promising and is expected to generate more therapeutic options for these diseases in the future.

Keywords: Arginine; Bezafibrate; Citrulline; EPI-743; Elamipretide; Epicatechin; Mitochondrial diseases; RP103; RTA 408.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / therapeutic use
  • Arginine / metabolism
  • Cardiolipins / drug effects
  • Catechin / therapeutic use
  • Clinical Trials as Topic*
  • Electron Transport / drug effects
  • Genetic Therapy
  • Humans
  • Liver Transplantation
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / pathology
  • Mitochondria / physiology
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / epidemiology
  • Mitochondrial Diseases / physiopathology
  • Mitochondrial Diseases / therapy*
  • Nitric Oxide / metabolism
  • Oxidative Phosphorylation
  • Triterpenes / therapeutic use


  • Antioxidants
  • Cardiolipins
  • Triterpenes
  • Nitric Oxide
  • Catechin
  • Arginine
  • omaveloxolone