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

Highlights

• Idebenone can partially compensate for the deleterious effect of the m.11778G > A mitochondrial DNA mutation.

• The beneficial effect of idebenone on mitochondrial function was only observed in a subgroup of patient-derived fibroblasts.

• Quinone analogues can have a detrimental effect on certain mitochondrial parameters when tested in vitro.

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.