Vitamin Switches on a Gene A Potential New Treatment for Friedreich's Ataxia?

Vitamin Switches on a Gene A Potential New Treatment for Friedreich's Ataxia?

Friedreich’s ataxia is a debilitating disease with no cure. A neurodegenerative condition that frequently takes hold in childhood, the inherited condition robs people of their co-ordination and motor functions over time. Speech becomes slurred, mobility impaired to the point of severe disability frequently by the age of 30, and sufferers are at a high risk of diabetes and cardiomyopathy. But novel research from the CSC holds promise for a new therapeutic approach, using a commonly available vitamin supplement to modify the epigenetic controls of the genetic defect causing the illness.

The symptoms of Friedreich’s ataxia are caused by a deficiency in the protein frataxin. A mutation that creates triplets of repeating DNA damages the gene that normally codes for the Frataxin protein, effectively silencing it. Research published in Human Molecular Genetics reveals how this process works, and suggests how it might be tackled. Richard Festenstein (Head of Gene Control Mechanisms and Disease) explains: “The gene silencing is characteristic of something called Position Effect Variegation (PEV) – an archetypal epigenetic phenomenon in which genes are silenced by heterochromatin, and which is sensitive to modifiers.” This realisation opens the door to a potential therapy. If the silencing mechanism can be reversed, expression of that gene could be returned to normal levels.
“We have identified a drug,” says Festenstein, “that switches this gene back on in cells in the correct tissues. In large doses, nicotinamide – vitamin B3 – might be able to restore frataxin levels two- to three-fold, up to asymptomatic levels.” This discovery is the culmination of over a decade’s work for Festenstein. “In 1996 we showed that PEV could happen in a mammal. In 2003 we showed that triplet repeats could induce this type of silencing in vivo in mice.” Now, applying that knowledge to Friedreich’s ataxia has yielded potentially exciting results.
“Nicotinamide is readily available and has a strong safety profile, as it’s already taken as a vitamin supplement,” says Festenstein. So how does it work? For heterochromatin to form, the histone proteins around which the DNA wraps must be methylated. For this to happen, first an acetyl group must be removed. By inhibiting an enzyme that removes the acetyl group, nicotinamide increases acetylation, and therefore lowers the methylation-reducing heterochromatinisation. “We found that the locus was in a more physically open structure after adding nicotinamide. That’s what you’d expect from a gene that is active.”
Reactivating the aberrantly silenced gene could be the key to countering the neurodegeneration experienced by people with Friedreich’s ataxia. Despite the potential, Festenstein remains cautious: “it’s important that patients don’t start taking the drug yet. We’re starting an exploratory clinical trial now, and hopefully that will give us a better idea of whether this could be an effective, safe and reliable treatment.” And this could be the beginning: “with the rise of next-generation sequencing it’s becoming easier to look at the DNA sequences around genes. This could be a prototype for many other diseases. It might be just the tip of the iceberg.”
Reference: Chan, P. K., Torres, R., Yandim, C., Law, P. P., Khadayate, S., Mauri, M., Grosan, C., Chapman-Rothe, N., Giunti, P., Pook, M., Festenstein, R., Mar. 2013. Heterochromatinization induced by GAA-repeat hyperexpansion in friedreich's ataxia can be reduced upon HDAC inhibition by vitamin b3. Human molecular genetics.

Positive news! Thank you...,;o)

Sounds very hopeful ! Thanks for sharing.

Is any of this applicable to Cerebellar ataxia? Neta

Good news and some hope for the FAs.

Any hope for us with CA yet?

This could be great news for people with FA, and i just hope they start putting more money into the sca,s

It would be nice to hear a medical response, as well as a response to the question of whether this "medication" or vitamin or whatever it is, is applicable to CA? N

Does anyboy know of an alternative the 'quinine sulphate' for cramps I think it may do more harm that good.

I've never heard of "quinine sulphate". I stretch my muscles each day, as well as eat a banana (contains potassium) which helps my cramps. I also get a full-body massage once each month. ;o)

Cramp is a big problem for me too. Try to keep warm and stretch as much as you can. I posted this on another forum and so I copied it here, in case it helps.

When I had my annual check-up in London a couple of years ago, they tried to get me on Baclofen to help it. It really works for lots of folk but I felt dreadful on it. I did a bit of research to try and find a herbal alternative.

You must be very careful that supplements do not mess up any other medication you are on. I found this good site to check things out on

For the cramp I take organic turmeric. 1 X 400mg in the morning and 1 at night. If I am having trouble with cramp, I have another at lunchtime (not very often)

I also take the equivalent of cod liver oil. For my particular type of ataxia (SCA1), it is better to take a vegetarian one.
I take 1 in the morning and 1 at night.

These definitely also help friends and relatives with bad arthritis too.

Hope it helps : )