Emerging therapies for mitochondrial disorders

Brain. 2016 Jun;139(Pt 6):1633-48. doi: 10.1093/brain/aww081. Epub 2016 May 3.


Mitochondrial disorders are a diverse group of debilitating conditions resulting from nuclear and mitochondrial DNA mutations that affect multiple organs, often including the central and peripheral nervous system. Despite major advances in our understanding of the molecular mechanisms, effective treatments have not been forthcoming. For over five decades patients have been treated with different vitamins, co-factors and nutritional supplements, but with no proven benefit. There is therefore a clear need for a new approach. Several new strategies have been proposed acting at the molecular or cellular level. Whilst many show promise in vitro, the clinical potential of some is questionable. Here we critically appraise the most promising preclinical developments, placing the greatest emphasis on diseases caused by mitochondrial DNA mutations. With new animal and cellular models, longitudinal deep phenotyping in large patient cohorts, and growing interest from the pharmaceutical industry, the field is poised to make a breakthrough.

Keywords: gene therapies; mitochondrial disorders; pharmaceuticals; protein; treatment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics
  • Disease Models, Animal
  • Drug Delivery Systems / methods
  • Humans
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / surgery
  • Models, Biological
  • Molecular Targeted Therapy / methods*
  • Mutation
  • Stem Cell Transplantation / methods


  • DNA, Mitochondrial