Reduction of interleukin-6 levels in patients with Friedreich's Ataxia treated with omaveloxolone.

BACKGROUND

Friedreich's Ataxia (FRDA) is the most common inherited spinocerebellar ataxia and is caused by a homozygous GAA trinucleotide repeat expansion in the frataxin (FXN) gene, leading to reduced intramitochondrial frataxin expression with a consequent progressive neurodegeneration and multisystem involvement. Neuroinflammatory pathways may contribute to FRDA pathophysiology and IL-6 represents a biologically relevant inflammatory mediator. Recently, omaveloxolone (Omav), an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, demonstrated clinically meaningful neurological benefits with a favorable safety profile.

OBJECTIVES

In this study, we report a 1-year follow-up of our real-life population treated with Omav, with a specific focus on clinical outcomes, safety, and inflammatory biomarkers.

METHODS

Twenty patients with FRDA were evaluated for 48 weeks using clinical scales (mFARS, SARA, FSS, and FA-ADL) and laboratory testing. Inclusion criteria were genetically confirmed FRDA, age ≥ 16 years and mFARS <80. All patients received Omav 150 mg/day.

RESULTS

Treatment showed a favorable safety profile, clinical stabilization and no serious adverse events with only one treatment discontinuation. IL-6 levels showed a progressive and significant reduction during follow-up. Transient hepatic enzyme elevations did not lead to treatment discontinuation.

CONCLUSIONS

Omav confirmed a favorable safety and tolerability profile in adult patients with FRDA in a real-world setting after 48 weeks of treatment. The sustained reduction in IL-6 levels further supports a potential direct immunomodulatory effect of the drug, consistent with its proposed disease-modifying activity. However, further long-term studies are warranted to better define the efficacy of Omav in FRDA.