Vitamin B3 may be key for treating Friedreich's ataxia

An essential vitamin commonly known for processing fat and proteins in the body may hold the key to slowing the progression of Friedreich’s ataxia, according to findings published today in The Lancet.

In the first clinical trial of its kind, researchers including BRC-supported Dr Paola Giunti tested the ability of nicotinamide (a form of vitamin B3) to increase levels of frataxin, a protein abnormally low in Friedriech’s ataxia.

In a collaborative effort research teams from UCL and Imperial College tested the effect of increasing doses of nicotinamide to determine how well it was tolerated and its safety profile. Patients received single and multiple doses of nicotinamide at doses much higher than used for vitamin supplementation. Nicotinamide was generally well tolerated and, when taken daily for up to two months, was shown to increase levels of frataxin protein to the levels found in carriers without symptoms of Friedriech’s ataxia.

In a previous study the team showed that nicotinamide-induced increase in frataxin levels was achievable in cells taken from patients and that the mechanism involved nicotinamide acting on the gene that causes Friedreich’s ataxia by ‘switching it back on’. The result is an increase in production of frataxin protein, and is thought to work by ‘opening up’ the gene making it accessible to the machinery which switches it on.

BRC-supported Dr Paola Giunti from the UCL Ataxia Centre said: “We have developed extensive expertise in trials for Friedreich’s ataxia and assembled the largest cohort of patients in Europe. We are excited by the prospects of nicotinamide potentially being developed into a treatment but it is important to remember that we still need to conduct further trials to confirm the safety over a longer time and to see whether the increase in frataxin actually results in improvements for patients. We are extremely grateful to all the patients who have taken part in this important pilot trial.”

Dr Vincenzo Libri, Head of Clinical Studies at the NIHR/Welcome Trust Imperial College Clinical Research Facility and first author of the paper, said: "Finding a cure for Friedreich’s ataxia is what every researcher in the field dreams about. We're absolutely thrilled by our preliminary results and the hope it offers for the future of patients with this devastating condition and their families. Our results help us understand the key elements of how nicotinamide may work and are important for translating the research from the laboratory into a clinical treatment. However, given the exploratory nature of our investigation, our results should be interpreted with caution and require further substantiation from larger confirmatory studies before we can make our vision of a cure a reality”.

Professor Richard Festenstein, Professor of Neurology at Imperial College who led the previous previous study, said: “These results are very encouraging and importantly offer the prospect of a future treatment for this incurable condition. Further studies are needed to determine the safety of high-dose nicotinamide with long-term administration and whether it can increase frataxin levels when given for longer periods. Then we need to know if this will prevent further clinical decline in patients with Friedreich’s ataxia. The study is also exciting because it provides proof-of-concept that aberrant gene silencing can be overcome in humans using an ‘epigenetic modifier’. This opens the way to a radical approach for other disorders caused by a similar mechanism.”

Sue Millman, Chief Executive Officer of Ataxia UK said: “We are really proud to have supported the basic science for this hugely exciting trial and to have moved the research forward to a human trial with such positive early findings. This study was a truly collaborative effort involving ataxia charities in four countries and a number of other funding bodies all recognizing the importance of the study. We now need to push forward towards a larger trial which we hope can eventually be translated into a treatment for patients. That is our goal.”

Friedreich’s Ataxia is a rare inherited disease that currently has no treatment or cure and that causes nervous system damage and movement problems.  The spinal cord and peripheral nerves degenerate, becoming thinner, and the cerebellum, the part of the brain that coordinates balance and movement, also degenerates.

This trial was funded by a grant from Ataxia UK in collaboration ataxia charities: Ataxia Ireland, Association suisse de l'Ataxie de Friedreich and Associazione italiana per la lotta alle sindromi atassiche. It was also supported by the National Institute of Health Research, the European Friedreich’s ataxia consortium for translational research and the Imperial College London  Biomedical Research Centre.

To read Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich’s ataxia: an exploratory, open-label, dose-escalation study in full click here.

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