Methylated and unmethylated epialleles support variegated epigenetic silencing in Friedreich ataxia

Layne N Rodden, Yogesh K Chutake, Kaitlyn Gilliam, Christina Lam, Elisabetta Soragni, Lauren Hauser, Matthew Gilliam, Graham Wiley, Michael P Anderson, Joel M Gottesfeld, David R Lynch, Sanjay I Bidichandani, Human Molecular Genetics, ddaa267, doi:10.1093/hmg/ddaa267

The higher prevalence in mild FRDA of somatic FXN epialleles devoid of DNA methylation is consistent with variegated epigenetic silencing mediated by expanded triplet-repeats. The proportion of unsilenced somatic FXN genes is an unrecognized phenotypic determinant in FRDA, and has implications for the deployment of effective therapies.

Omaveloxolone: potential new agent for Friedreich ataxia

David R Lynch and Joseph Johnson; Future Medicine, Neurodegenerative Disease Management 0 0:0 Published Online:12 Jan 2021 doi:10.2217/nmt-2020-0057

In this work, we review the evidence for use of omaveloxolone in FRDA from recent clinical trials. Though not at present approved for any indication, the present data suggest that this agent acting though increases in Nrf2 activity may provide a novel therapy for FRDA.

Dimethyl fumarate dose-dependently increases mitochondrial gene expression and function in muscle and brain of Friedreich’s ataxia model mice

Chun Kiu Hui, Elena N Dedkova, Claire Montgomery, Gino Cortopassi, Human Molecular Genetics, , ddaa282, doi:10.1093/hmg/ddaa282 

We observed significant decreases of multiple mitochondrial parameters, including deficits in brain mitochondrial Complex 2, Complex 4, and aconitase activity, supporting the idea that frataxin deficiency reduces mitochondrial gene expression, mitochondrial functions and biogenesis. 110 mg/kg oral DMF rescued these enzyme activities in brain and rescued frataxin and cytochrome oxidase expression in brain, cerebellum and quadriceps muscle of the FXNKD mouse model. Taken together, these results support the idea of using fumarate-based molecules to treat Friedreich’s ataxia or other mitochondrial diseases.

NAF Supports FARA’s Call to Action

January 15, 2021; Friedreich’s Ataxia Research Alliance (FARA) is encouraging Reata Pharmaceuticals to submit a New Drug Application (NDA) for Omaveloxolone, which recently completed a Phase III clinical trial as a treatment for Friedreich’s Ataxia (FA). FARA is also urging the Food and Drug Administration (FDA) to consider approving the NDA. FARA has prepared a letter that will be submitted to Reata Pharmaceuticals and the FDA; they are looking for supporters to sign the letter. NAF submitted a letter of support. To date, FARA has received more than 40,000 signatures from patients, their family and friends, and rare disease advocates. We want you to sign on too!