Multiple Sclerosis Therapy Tecfidera Could Also Help Mitochondrial Disease, Friedreich’s Ataxia Patients, Study Finds

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by Magdalena Kegel |

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Tecfidera (dimethyl fumarate), an oral drug used to treat multiple sclerosis (MS), could also benefit mitochondrial disease patients as well as those with Friedreich’s ataxia (FA), concludes two studies from the University of California, Davis School of Veterinary Medicine.

The first study, “Dimethyl fumarate mediates Nrf2-dependent mitochondrial biogenesis in mice and humans,” was led by Dr. Gino Cortopassi, a UC Davis biochemist and professor who has researched mitochondrial diseases for the past 25 years. It showed that the drug increased mitochondria by acting on a factor called Nrf2 — a transcription factor or molecule that controls the activity of genes. Tecfidera activated mitochondrial genes, which boosted production of mitochondria in MS patients. The research team noted the same effects of Tecfidera when they treated human lab-grown skin cells and mice.

Low mitochondrial numbers are a consequence of a loss of the protein frataxin, which causes FA, researchers found in the second study, “Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans.”  The two discoveries — both of which appeared in the journal Human Molecular Genetics — suggest that Tecfidera could benefit patients with FA and other mitochondrial and muscle conditions.

“Taken together, these findings suggest that DMF [dimethyl fumarate], by increasing mitochondria, has the potential to lessen the symptoms of muscle diseases, which are caused at least in part by mitochondrial abnormalities,” Cortopassi said in a news release written by Pat Bailey.

But the findings might also have other implications. Although researchers have long known that frataxin is a mitochondrial protein, they have not understood how its loss causes the disease, in which both muscles and neurons weaken and die. Scientists can use the insight that healthy mitochondria production depends on frataxin to develop mitochondrial measurements as a disease biomarker, according to Cortopassi.

“Knowing now that the frataxin deficiency causes a shortage of mitochondria, we and others may be able to use the number of mitochondria as a biomarker for determining the disease severity and progression in Friedreich’s ataxia patients,” he said. “Such a biomarker could also be used to evaluate the effectiveness of new drugs for treating the disease.”

In 2011, Cortopassi established Ixchel Pharma to find treatments for mitochondrial diseases using drugs already on the market. Several researchers who specialize in mitochondrial disease and neurology praised the latest studies.

“This represents groundbreaking work that provides an important contribution to understanding the pathology of both Friedreich’s ataxia and mitochondrial diseases,” said Dr. Mike Murphy, principal investigator of the MRC Mitochondrial Biology Unit at England’s University of Cambridge.

“The advances in these two papers are exciting because they suggest that a current drug could be used to treat FA and mitochondrial DNA diseases, for which there are few therapies,” he added.

Added Dr. Franco Taroni, a researcher at Italy’s Carlo Besta Neurological Institute: “Given the amount of time and money nowadays required for developing brand-new drugs, discovering a new use for a molecule for which detailed clinical information is already available clearly represents a major, if not the only, hope for people affected by an orphan disease.”