nicotinamide-beta-riboside and Ataxia-Telangiectasia

A first study on nicotinamide riboside treatment of 24 individuals with ataxia telangiectasia with a mean age of 17.5 years showed improved ataxia scores and immunoglobulin levels. We here present the effect of nicotinamide riboside in another individual with ataxia and recurrent infections in whom treatment started as early as at the age of 3 years and 6 months.During 11 months of follow-up, mean total Scale-for-the-Assessment-and-Rating-of-Ataxia decreased from 27 to 9 points and mean total Score for the Gross-Motor-Function-Measure increased from 61 to 78%. Improvement in drawing skills was observed by ICF-based ergotherapeutic examination. Use of antibiotics and frequency of hospitalizations due to infections were reduced by more than 90%. Immunological parameters in blood remained unchanged. No adverse effects occurred.While the effects on motor and speech improvement might be partly explained by development, our study replicates the previous finding of a positive effect of nicotinamide riboside treatment in ataxia telangiectasia. One could even hypothesize that the early treatment will lead to even better outcome. Given the absence of adverse effects, we strongly encourage to consider nicotinamide riboside in all individuals with ataxia telangiectasia.

Topics: Adolescent; Ataxia; Ataxia Telangiectasia; Child, Preschool; Humans; Niacinamide; Pyridinium Compounds

Treatment of animal models with ataxia telangiectasia (A-T) with nicotinamide riboside (NR) improved their neurological outcome and survival.. The aim of this study is to investigate the effects of NR in patients with A-T.. 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.. 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.. 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.

Topics: Animals; Ataxia Telangiectasia; Humans; Immunoglobulins; Niacinamide; Pyridinium Compounds; Quality of Life

Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A-T). Loss of mitochondrial function can drive age-related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in A-T patient fibroblasts, and in ATM-deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD

Topics: Animals; Ataxia Telangiectasia; Ataxia Telangiectasia Mutated Proteins; Case-Control Studies; Cell Line, Tumor; Dietary Supplements; Disease Models, Animal; Female; Fibroblasts; Humans; Male; Membrane Proteins; Mice; Mice, Knockout; Mitochondria; Mitophagy; NAD; Neurons; Niacinamide; Pyridinium Compounds; Rats; Rats, Sprague-Dawley; Senescence-Associated Secretory Phenotype; Signal Transduction; Transfection; Treatment Outcome