Effects of Nicotinamide Riboside (Vitamin B3) in Patients With Ataxia Telangiectasia.

Rationale: Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder, with a high cancer risk, that also affects the immune and respiratory system. Therapy for A-T is restricted to symptomatic treatment including rehabilitation care, combined with infection prevention and treatment, and screening for pulmonary dysfunction and malignancies. A-T is caused by mutations in the ATM gene. The ATM protein plays a pivotal role in more than 100 different biochemical processes, among which cellular energy metabolism, cell signaling, and DNA repair. Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in many of these processes and studies have shown that NAD+ deficiency plays a role in disease mechanisms underlying DNA repair disorders such as A-T. NAD+ is available in food, but can also be synthesized in the body from its precursors nicotinamide, nicotinic acid, and nicotinamide riboside (NR), as a group called "vitamin B3". Treatment of experimental A-T animal models with NR showed beneficial effects. The aim of this study is to investigate whether treatment with NR during a period of six months may have positive effects on the disease course of patients with A-T.

Objective: To investigate the effects of NR on the disease course of patients with ataxia telangiectasia.

Study design: Single center, interventional, explorative, open-label proof of concept study.

Study population: Patients with A-T (age >2 years).

Intervention (if applicable): Patients will be treated with nicotinamide riboside (25mg/kg/day), during four consecutive months, followed by a washout period of two months.