CNS Drugs. 2026 Jun 29. doi: 10.1007/s40263-026-01312-w. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVE: Friedreich ataxia is a multi-system neurodegenerative disorder with frequent cardiac and metabolic involvement. Omaveloxolone, the first approved therapy for Friedreich ataxia, improves neurological outcomes through nuclear factor erythroid 2-related factor 2 activation and exerts measurable systemic effects. However, its effects on lipid metabolism have not been systematically assessed. The present study aimed to systematically evaluate the longitudinal effects of omaveloxolone on serum lipid parameters in a real-world cohort of patients with Friedreich ataxia over a 12-month observation period.
METHODS: We conducted a retrospective, single-center, real-world observational study in adults with genetically confirmed Friedreich ataxia newly treated with omaveloxolone (150 mg/day). Serum lipid parameters, including total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, very low-density-lipoprotein cholesterol, triglycerides, C-reactive protein, apolipoprotein A-I, and apolipoprotein B (ApoB), were measured at baseline and after 1, 2, 3, 6, and 12 months. Longitudinal changes were analyzed using frequentist and Bayesian linear mixed-effects models.
RESULTS: A total of 17 patients were included in the analysis (13 male [76%]; mean age 36.1 years [range 20-55]; mean disease duration 17.4 years [range 6-33 years]). Total cholesterol increased shortly after treatment initiation and remained elevated throughout the follow-up period, driven almost entirely by a sustained rise in low-density lipoprotein-cholesterol (+ 35-50 mg/dL) and ApoB (+ 20-25 mg/dL) levels, whereas high-density lipoprotein-cholesterol, apolipoprotein A-I, very low-density-lipoprotein cholesterol, and triglyceride levels remained stable. Low-density lipoprotein-cholesterol and ApoB levels were strongly correlated at all timepoints (r = 0.83-0.95). The total cholesterol/high-density lipoprotein-cholesterol ratio increased by approximately one unit and persisted throughout the follow-up period.
CONCLUSIONS: In this real-world Friedreich ataxia cohort, omaveloxolone treatment was associated with a sustained shift toward a more atherogenic lipid profile, driven almost entirely by increased low-density lipoprotein-cholesterol and ApoB levels. This pattern is consistent with impaired hepatic clearance of ApoB-containing particles rather than increased production, supporting routine lipid monitoring and further evaluation of long-term cardiovascular risk.
PMID:42371397 | DOI:10.1007/s40263-026-01312-w