Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy

Mitochondrion. 2017 Sep:36:36-42. doi: 10.1016/j.mito.2017.01.004. Epub 2017 Jan 16.

Abstract

Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness among young adults. In this study, we investigated the potential of four quinone analogues (CoQ1, CoQ10, decylubiquinone and idebenone) in compensating for the deleterious effect of the m.11778G>A mitochondrial DNA mutation. The LHON fibroblast cell lines tested exhibited reduced cell growth, impaired mitochondrial bioenergetics and elevated levels of reactive oxygen species (ROS). Idebenone increased ATP production and reduced ROS levels, but the effect was partial and cell-specific. The remaining quinone analogues had variable effects and a negative impact on certain mitochondrial parameters was observed in some cell lines.

Keywords: Coenzyme Q(10); Idebenone; Leber hereditary optic neuropathy; Mitochondrial disease; Optic atrophy; Quinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Adolescent
  • Antioxidants / metabolism*
  • Cells, Cultured
  • Energy Metabolism / drug effects
  • Fibroblasts / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Optic Atrophy, Hereditary, Leber / pathology*
  • Quinones / metabolism*
  • Reactive Oxygen Species / analysis*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / metabolism
  • Young Adult

Substances

  • Antioxidants
  • Quinones
  • Reactive Oxygen Species
  • Ubiquinone
  • Adenosine Triphosphate
  • idebenone