Functional impact of Nicotinamide Riboside on the immune system of patients with A-T
Research Project information
Principal researcher: Dr Mirjam van der Burg
Institute: Leiden University Medical Center, Netherlands
Cost: £250,000 over 36 months in partnership with AEFAT (Spain) and BrAshA-T (Australia)
Start Date: 1st of September 2024
What are the researchers proposing to do?
Ataxia telangiectasia (A-T) is a neurodegenerative disorder with immunodeficiency and cancer predisposition. Recently, Dr van der Burg and others have showed that Nicotinamide Riboside (NR) has positive effects on the disease course of A-T. NR is a variant of vitamin B3 and has limited side effects. Many studies have already focused on how NR influences the neurological system but in this project, the team will investigate the effect of NR on the immune system in patients with A-T. In addition, they will study the natural course of development of immune parameters in patients with an early diagnosis of A-T, because they hypothesize that NR treatment may have greater benefits for patients with an early diagnosis. Finally, the team will develop a new model system to test the influence of NR and other potential treatment candidates on ATM-deficient immune cells.
Why?
This project will generate new insights into the natural course of the (mal)development of the immune system in the first year of life in A-T and will contribute to the exploration of potential benefits of NR for early diagnosed patients with A-T. The likely clinical impact is that NR is a new potential therapeutic agent that (also) has a positive effect on the immune system of (young) patients with A-T. In addition, a newly developed model system for immune cells can potentially be used for screening many other, new candidate drugs in the future.
How will the research be done?
The team will initiate an international survey to collect data on the clinical status and immunophenotype of patients with A-T diagnosed via new-born screening from medical electronic patient dossiers (EPD) to create a roadmap of the natural course of immune parameters during the first years of life. They will then use laboratory culture systems, which have been proven effective models for the immune system, in combination with ATM inhibitors and different doses of NR to investigate the impact of NR on the immune system. Finally, they will develop a new model system for ATM-deficient immune cells that is based on stem cells from cord blood in which an ATM mutation has been created via a state-of-the-art technique called CRISPR-based-gene editing.
How could it make a difference in the lives of those affected by A-T?
This project could make a significant difference to the lives of those affected by A-T, because more insights will be gained on the effect of NR on the immune system and as such add crucial knowledge to future (international) clinical trials on NR as a new candidate drug for improvement of both neurological and immunological clinical manifestations of the condition.
