Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich's Ataxia.

ABSTRACT: Friedreich's Ataxia (FA) is an inherited neurodegenerative disorder resulting from decreased expression of the mitochondrial protein frataxin, for which there is no approved therapy. High throughput screening of clinically used drugs identified Dimethyl fumarate (DMF) as protective in FA patient cells. Here we demonstrate that DMF significantly increases frataxin gene (FXN) expression in FA cell model, FA mouse model and in DMF treated humans. DMF also rescues mitochondrial biogenesis deficiency in FA-patient derived cell model. We further examined the mechanism of DMF's frataxin induction in FA patient cells. It has been shown that transcription-inhibitory R-loops form at GAA expansion mutations, thus decreasing FXN expression. In FA patient cells, we demonstrate that DMF significantly in

SUBMITTER: Jasoliya M 

PROVIDER: S-EPMC6546270 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature