Sub Subramony, MD, discusses the directions that Friedreich’s ataxia research is taking in finding new avenues of treatment.

The future of therapeutic research in Friedreich’s ataxia, I think, is very hopeful. I make the point that one of the advantages of having a single-gene disorder — like a monogenic disease like Friedreich’s ataxia — is that we now know the disease is coming from that one gene abnormality, that single gene. You’re able to understand the pathogenesis and the pathophysiology in these diseases much better than some of the other illnesses where you don’t have a single-gene basis. Some of the other degenerative disorders — for example, a lot of patients with ALS — we don’t know where it starts.

I think there are a number of strategies that are either in Phase 1 trials or just coming up, that actually target the gene itself or the protein. So there’s exciting trials of protein replacement — the ability to just put the frataxin back into the system is being investigated, and trials are on the way. There are all kinds of molecules, including synthetic molecules, that are able to push the abnormal gene to make more protein. And this is very exciting. This is actually in Phase 1 trial right now, with what’s called synthetic transcription elongation factors.

There are probably strategies, such as even replacing the messenger RNA, that are in the laboratory stage.

And of course, everybody is interested in direct gene replacement. So, a number of labs, including one here at the University of Florida, has the frataxin gene in a vector, which is traditionally what we call AAV, or adeno-associated virus vector. The work is going on to understand the various barriers that exist for this approach.

Of course the idea would be, of course, if you are able to inject this virus with the gene in it, and then be able to get it into all the parts of the body that it’s needed — for example, the heart, the pancreas, various parts of the brain, the cerebellum, and the spinal cord — you should be able to turn on the protein production and hopefully be able to arrest the disease, and if you get it early enough, maybe prevent it from deteriorating as well. So, this is the hope that we have, but there are still a number of barriers.

And so, this is very exciting news — that we are now in the phase of research where the research is actually targeting the gene in multiple ways to improve the function of the gene.