Long‐Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia

Abstract

BackgroundSupplementation of nicotinamide riboside (NR) ameliorates neuropathology in animal models of ataxia telangiectasia (A‐T). In humans, short‐term NR supplementation showed benefits in neurological outcome.ObjectivesThe study aimed to investigate the safety and benefits of long‐term NR supplementation in individuals with A‐T.MethodsA single‐arm, open‐label clinical trial was performed in individuals with A‐T, receiving NR over a period of 2 years. Biomarkers and clinical examinations were used to assess safety parameters. Standardized and validated neuromotor tests were used to monitor changes in neurological symptoms. Using generalized mixed models, test results were compared to expected disease progression based on historical data.ResultsNAD+ concentrations increased rapidly in peripheral blood and stabilized at a higher level than baseline. NR supplementation was well tolerated for most participants. The total scores in the neuromotor test panels, as evaluated at the 18‐month time point, improved for all but one participant, primarily driven by improvements in coordination subscores and eye movements. A comparison with historical data revealed that the progression of certain neuromotor symptoms was slower than anticipated.ConclusionsLong‐term use of NR appears to be safe and well tolerated, and it improves motor coordination and eye movements in patients with A‐T of all ages. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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“…Recent clinical studies have demonstrated the benefits of NAD + supplementation to neurological conditions. NR supplementation has been shown to improve coordination and eye movement in patients with ataxia telangiectasia (Presterud et al., 2023 ), increase cerebral NAD + levels associated with altered brain metabolism and clinical improvement (Brakedal et al., 2022 ), and stimulate mitophagy which reverses memory impairment in nematodes, mice, and human cells (Fang, Hou, Palikaras, et al., 2019 ). These studies highlight the potential for NAD + supplementation as a therapeutic intervention and hint at the possibility for additional benefits from dual KP suppression and NAD + supplementation in the treatment of neurodegenerative diseases.…”

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“…Following the previous findings that hyper PARylation-induced depletion of NAD + is associated with accelerated aging in ATM -deficient C elegans and mouse models ( 23 ), her lab has conducted a 2-year clinical study on the effect of supplementation of an NAD + precursor NR in ataxia-telangiectasia (A-T) patients, a rare genetic disorder with premature aging features. She reported that NR improves neuro-motor function in A-T patients and may also delay disease progression when compared to historical control groups ( 24 ). These findings offer promise for potential clinical interventions for neurodegenerative diseases driven by DNA damage response and genomic instability.…”

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“…Moreover, drugs to slow disease progression are currently being explored in clinical trials. Nicotinamide riboside and NAD supplementation is a promising candidate treatment, where supplementation has been associated with improved performance on neurological and motor tests [44].…”