CLINICAL TRIAL OF A TREATMENT OF FRIEDREICH'S ATAXIA The use of Idebenone in the treatment for Friedreich's Ataxia Since November 1999, we began a pilot study to evaluate the efficacy and the side effects of Idebenone in eleven children and teenagers affected by FA, followed at Marie-Enfant Hospital in Montreal. We have analyzed the evaluations of those children. Ten adults are still undergoing treatment at the University of Montreal Health Center and their evaluations are not completed yet. Freidreich's Ataxia is a hereditary disease with an onset during childhood or adolescence and that is characterized by balance and coordination problems (ataxia) associated with a thickening and a weakening of the function of the cardiac muscle (cardiomyopathy). This disease results from the marked reduction in the production of frataxin in the cells of the affected individuals. This decrease in frataxin leads to an accumulation of iron in the mitochondria, especially in the nervous system and the heart. The mitochondrias are structures that generate energy in the cell and that can be compared to the carburetor in a car. When the mitochondrias do not function properly, it leads to a raise of the levels on certain products in the blood, including malondialdehydes that we measured throughout the study. After having considered different approaches to increase mitochondrial function, we decided to study Idebenone in about twenty patients affected by FA. We chose that medication for different reasons. First, we knew that French researchers had used Idebenone with some success (especially at the cardiac level) in three patients affected by FA. Furthermore, we knew that this medication had cause an amelioration in patients affected by Alzheimer's disease, without causing any side effects, which led us to believe that Idebenone could act in the central nervous system without significant toxicity risks. We gave a daily dose of Idebenone of 5 mg per kilogram per day to eleven children or teenagers affected by FA. They were evaluated systematically before starting treatment, and every three months until the end of the treatment. This evaluation included a medical visit, a thorough cardiologic evaluation, functional tests to measure balance and coordination, blood malondialdehyde dosage and finally blood and urine tests to make sure there were no toxic effects from the medication. After one year of treatment, those repeated evaluation enabled us to observe either a slight amelioration or a stability of the cardiac function in all the children or teenager treated, which is very significant since we would have expected a deterioration of the cardiac function during that period. Balance and coordination problems were stable in eight patients and worsened in the three others. The blood levels of malondialdehyde stayed high in all the children or teenagers. Thus, Idebenone does not have major effects on ataxia or the function of mitochondria, at least not at this dose. However, the fact that eight of the eleven patients were stable could indicate a partial efficacy of the drug. Finally, we did not observe any side effects or toxic effects of Idebenone in patients. Although the results are not spectacular, we think the study on Idebenone needs to be continued since it is the first medication that cause an amelioration (even though mainly at the cardiac level) in FA. In the next few weeks, we will discuss with experts about the possibility of raising the daily dosage of Idebenone in the treated children and teenagers, or to combine this medication with another medication that could increase mitochondrial function and a way that would be complementary to Idebenone. Text written by Michel Vanasse, neurologist Translated by Fanny Chagnon These people participated in the study at Saint-Justine's and Marie-Enfant Hospitals in Montreal, Canada. Ms. Denyse Bernard, occupational therapist. Ms. Louise Chicoine, physical therapist. Ms. Monique Émond, physical therapist and research assistant. Dr. Anne Fournier, cardiologist. Dr. Guy Lepage, researcher in nutrition and gastro-enterology. Dr. Massimo Pandolfo, neurologist and head of the project. Dr. Michel Vanasse, neurologist.