Vitamin B3 may be useful in treating the inherited neurological disease Friedreich's ataxia, new findings suggest.

Friedreich’s ataxia is a debilitating disease with no cure. It typically takes hold in childhood and robs people of their coordination and motor functions over time. Speech becomes slurred and mobility impaired to the point of severe disability, often by the age of 30, and sufferers are at a higher risk of diabetes and heart disease.

New research at Imperial College London suggests that vitamin B3, an essential nutrient found in many meats and vegetables, can restore levels of a protein that is deficient in Friedreich’s ataxia patients.

The disease’s symptoms are a result of the body underproducing a protein called frataxin. In Friedreich’s patients, the gene that codes for frataxin is abnormally expanded, containing hundreds or thousands of repeating triplets – blocks of three letters of DNA code – which switch off the frataxin gene.

The new study, published in Human Molecular Genetics, has shed light on how this happens and how it might be tackled. The researchers found that the repeating letters make the DNA become tightly coiled, making it impossible to read the code that carries instructions for making the protein. This discovery suggested that molecules that affect DNA packaging – such as vitamin B3 – might help restore levels of frataxin to normal levels.

The study was led by Professor Richard Festenstein, from the Department of Medicine, in association with the MRC Clinical Sciences Centre. “We have identified a treatment that switches this gene back on in cells in the correct tissues,” Professor Festenstein said. “In large doses, vitamin B3 might be able to restore frataxin levels two- to three-fold, which should bring symptoms under control. It’s already taken as a vitamin supplement so it should be very safe.”

The discovery is the culmination of over a decade’s work for Professor Festenstein, who showed in 1996 that DNA could be silenced in mammals as a result of repeating triplets in the genetic code.

He is exploring the hypothesis that reactivating the silenced gene could be the key to countering the neurological symptoms experienced by people with Friedreich’s ataxia. However, more research will be needed to confirm if this is the case.

“We’re not recommending that patients should start taking vitamin B3 right now,” Professor Festenstein said. “We’ve started an exploratory clinical trial, and hopefully that will give us a better idea of whether this could be an effective, safe and reliable treatment.

“With the rise of next-generation sequencing, it’s becoming easier to look at the DNA sequences around genes. There may be many other diseases where gene expression is being affected in a similar way. It might be just the tip of the iceberg.”

The research was funded by Imperial College London, the Medical Research Council, Ataxia UK and the European Friedreich's Ataxia Consortium for Translational Studies (EU EFACTS).

Reference

Chan, P.K., Torres, R., Yandim, C., Law, P.P., Khadayate, S., Mauri, M., Grosan, C., Chapman-Rothe, N., Giunti, P., Pook, M., et al. (2013). Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum. Mol. Genet. (2013) 22 (13):2662-2675.doi: 10.1093/hmg/ddt115