Nicotinamide Riboside Improves Ataxia Scores and Immunoglobulin Levels in Ataxia Telangiectasia

. 2021 Sep 13.
 doi: 10.1002/mds.28788. Online ahead of print.

Nicotinamide Riboside Improves Ataxia Scores and Immunoglobulin Levels in Ataxia Telangiectasia

Stefanie J G Veenhuis12, Nienke J H van Os23, Anjo J W M Janssen4, Marjo H J C van Gerven4, Karlien L M Coene5, Udo F H Engelke5, Ron A Wevers5, Gerjen H Tinnevelt6, Rob Ter Heine78, Bart P C van de Warrenburg239, Corry M R Weemaes1, Nel Roeleveld810, Michèl A A P Willemsen12911
Affiliations 

Affiliations

  • 1Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 2Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 3Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 4Department of Rehabilitation, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 5Department of Laboratory Medicine, Translation Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 6Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
  • 7Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 8Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 9Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 10Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
  • 11Department of Pediatric Neurology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

Background: Treatment of animal models with ataxia telangiectasia (A-T) with nicotinamide riboside (NR) improved their neurological outcome and survival.

Objective: The aim of this study is to investigate the effects of NR in patients with A-T.

Methods: In this open-label, proof-of-concept study, 24 patients with A-T were treated with NR during four consecutive months. The effects of NR on ataxia, dysarthria, quality of life, and laboratory parameters were analyzed.

Results: During treatment, ataxia scores improved; mean total Scale for the Assessment and Rating of Ataxia and International Cooperative Ataxia Rating Scale scores decreased to 2.4 and 10.1 points, respectively. After NR withdrawal, ataxia scores worsened. In immunodeficient patients, the mean serum IgG concentration increased substantially until the end of the study period with 0.52 g/L. Untargeted metabolomics analysis revealed increased plasma levels of NR metabolites and purine nucleosides during treatment. Adverse effects did not occur.

Conclusions: Treatment with NR is tolerated well and associated with improvement in ataxia and serum immunoglobulin concentrations in patients with A-T. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: A-T mutated gene; ataxia telangiectasia; nicotinamide riboside.