CAFA is launching a major research project

Development of a potential therapy for Friedreich ataxia based on transduction of the frataxin protein in the mitochondria

Friedreich ataxia is caused by a mutation of the frataxin gene.  This mutation triggers a decrease in the production of frataxin in all the patient’s cells.  Frataxin plays an important role in the metabolism of iron at the mitochondrial level and its reduction brings about the death of many cells in the brain, heart, muscles and pancreas.  This cell death is responsible for the many symptoms of the illness.

This research project’s goal is to develop a therapy for Friedreich ataxia by targeting the actual cause of the illness, the reduction of frataxin.  The project will therefore aim to administer the frataxin protein intravenously.  However, as this protein does not spontaneously penetrate cells, it will be encapsulated with peptides (fragments of other proteins), in nanoparticles.  Alternatively, the frataxin protein itself will be modified by adding peptides which will allow the proteins to penetrate not only the interior of cells, but also the interior of the mitochondria.

The experiments will be initially conducted on patient cells.  This will allow experimenters to determine which method will best allow the frataxin to enter not only the cells, but also the mitochondria.  Experimenters will therefore be able to confirm that the increase of frataxin can resolve the problems of Friedreich ataxia at the cellular level.  Following this, experiments will be conducted on mice that do not produce enough frataxin and who therefore develop symptoms of the illness.  As the illness affects many muscles and organs, to develop an effective treatment, it is necessary to deliver frataxin to all of these tissues.  This will be done by injecting the encapsulated frataxin, or the frataxin joined with a peptide, intravenously.  We will confirm that the frataxin reaches all of these tissues, that it penetrates the cells, and especially, when it is administered repeatedly, that is prevents the development of this illness in mice.

This type of therapy is based on the replacement of the missing protein.  This therapeutic approach is already used in the treatment of many illnesses.  In fact, the company Genzyme already markets Myozyme (alpa-glocosidase acid) to treat Pompe disease, Fabrazyme (alpha-galactosidase) for Fabry disease, Aldurazyme (Iuronidase) for Hurler syndrome, and Cerezyme (Imiglucerase, a recombinant glucocerbrosidase) for Gaucher’s disease.  Cerezyme has been used clinically for 15 years and is administered to 4000 patients worldwide.  How long must we wait for a treatment for Friedreich ataxia with frataxin?

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This research project will be conducted under the direction of Mr. Jacques P. Tremblay, Ph.D., professor in the Department of Molecular Medicine of Laval University in Quebec and main investigator at the Research Centre of Quebec city (CHUL). The project duration is two (2) years at a cost of 240, 000 dollars.

The CAFA - Claude St-Jean Foundation's mission is to advance research on familial ataxias, to intervene on both the root causes and the effects of ataxias and generate funds through fundraising campaigns, activities, voluntary subscriptions, grant applications, sponsorships, bequests. Founded in 1972 by Claude St-Jean, CAFA has invested nearly $ 15 million in present value in scientific research.

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