Lynch DR; Mathews KD; Perlman S; Zesiewicz T; Subramony S; Omidvar O; Vogel AP; Krtolica A; Litterman N;
van der Ploeg L; Heerinckx F; Milner P; Midei M;

Journal of neurology [J Neurol] 2022 Dec 03.
Date of Electronic Publication: 2022 Dec 03.

Objectives: Friedreich ataxia is (FRDA) an autosomal recessive neurodegenerative disorder associated with intrinsic oxidative damage, suggesting that decreasing lipid peroxidation (LPO) might ameliorate disease progression. The present study tested the ability of RT001, a deuterated form of linoleic acid (D2-LA), to alter disease severity in patients with FRDA in a double-blind placebo-controlled trial.
Methods: Sixty-five subjects were recruited across six sites and received either placebo or active drug for an 11-month study. Subjects were evaluated at 0, 4, 9, and 11 months, with the primary outcome measure being maximum oxygen consumption (MVO2) during cardiopulmonary exercise testing (CPET). A key secondary outcome measure was a composite statistical test using results from the timed 1-min walk (T1MW), peak workload, and MVO2.
Results: Forty-five subjects completed the protocol. RT001 was well tolerated, with no serious adverse events related to drug. Plasma and red blood cell (RBC) membrane levels of D2-LA and its primary metabolite deuterated arachidonic acid (D2-AA) achieved steady-state concentrations by 4 months. No significant changes in MVO2 were observed for RT001 compared to placebo. Similarly, no differences between the groups were found in secondary or exploratory outcome measures. Post hoc evaluations also suggested minimal effects of RT001 at the dosages used in this study.
Interpretations: The results of this study provide no evidence for a significant benefit of RT001 at the dosages tested in this Friedreich ataxia patient population.