Therapeutic Potential of Dimethyl Fumarate to Treat Friedreich Ataxia: Francesco Saccà, MD, PhD


The associate professor of neurology at the University of Naples provided context on the mechanism of action for dimethyl fumarate and why there’s belief it can benefit patients with Friedreich ataxia. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"Dimethyl fumarate is also able to increase frataxin expression in FA in a specific way so that it's linked to the silencing of the gene. It enhances expression. There is a high chance that in patients with FA, we might even see a higher increase after dimethyl fumarate."

Friedreich ataxia (FA), an autosomal recessive neurodegenerative disorder, is the most common hereditary ataxia among persons of European ancestry. Therapeutic strategies for the disease include increasing frataxin protein and/or FXN/mRNA levels and replacing frataxin function. In 2023, the field saw its first approval for a therapy, with the FDA greenlighting omaveloxolone (Skyclarys; Biogen), a Nrf2 inhibitor. This medication restores mitochondrial function ex vivo in fibroblasts from patients with FA, but there is no evidence to suggest it can increase the levels of FXN gene expression and frataxin protein.

In the months following omaveloxolone’s approval, a group of investigators announced the design and protocol for a double-blind, placebo-controlled study to assess dimethyl fumarate, an FDA-approved medicine for relapsing multiple sclerosis, in patients with FA. Led by Francesco Saccà, MD, PhD, an associate professor of neurology at the University of Naples, the study aims to investigate whether this therapy can increase the expression of the FXN gene and frataxin protein and ameliorate in-vivo detectable measures of mitochondrial dysfunction in FA. The study is comprised of 2 main phases: a 12-week double-blind period followed by an additional 12-week extension phase.

In an interview with NeurologyLive®, Saccà discussed the idea behind the study and the reasons to assess dimethyl fumarate. He spoke on the mechanism of action of the therapy, the research that led up to this point, and some of the intricacies about the study. He also spoke on the fact that omaveloxolone’s ability to improve patients’ condition without impacting frataxin has opened the door for other potential therapies to hopefully do the same.

1. Pane C, Marra AM, Aliberti L, et al. Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety, and tolerability of dimethyl fumarate in Friedreich ataxia (DMF-FA-201). Front Neurosci. 2023;17:1260977. doi:10.3389/fnins.2023.1260977
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