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

. 2023 Oct 29.
 doi: 10.1002/mds.29645. Online ahead of print.

 

Rebecca Presterud1, Wei Hai Deng23, Anna Berit Wennerström4, Trudy Burgers5, Bharat Gajera6, Kirsten Mattsson5, Agnes Solberg5, Evandro F Fang147, Anni I Nieminen6, Asbjørg Stray-Pedersen58, Hilde Nilsen1479
Affiliations 
    • PMID: 37899683
 

Abstract

Background: Supplementation 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.

Objectives: The study aimed to investigate the safety and benefits of long-term NR supplementation in individuals with A-T.

Methods: A 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.

Results: NAD+ 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.

Conclusions: Long-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.

Keywords: ataxia telangiectasia; niagen; nicotinamide riboside.

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References

    1. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature 1988;336(6199):577-580.
    1. McGrath-Morrow SA, Rothblum-Oviatt CC, Wright J, Schlechter H, Lefton-Greif MA, Natale VA, et al. Multidisciplinary Management of Ataxia Telangiectasia: current perspectives. J Multidiscip Healthc 2021;14:1637-1644.
    1. Aguado J, Gómez-Inclán C, Leeson HC, Lavin MF, Shiloh Y, Wolvetang EJ. The hallmarks of aging in ataxia-telangiectasia. Ageing Res Rev 2022;79:101653.
    1. Petley E, Yule A, Alexander S, Ojha S, Whitehouse WP. The natural history of ataxia-telangiectasia (A-T): a systematic review. PloS One 2022;17(3):e0264177.
    1. Kim ST, Lim DS, Canman CE, Kastan MB. Substrate specificities and identification of putative substrates of ATM kinase family members. J Biol Chem 1999;274(53):37538-37543.