The Friedreich's Ataxia Research Alliance (FARA) and the National Institutes of Health (NIH) have just hosted the Third International Friedreich's Ataxia (FRDA) Scientific Conference at the NIH in Bethesda, Maryland, highlighting and advancing the exciting research leading now to a variety of clinical trials that show promise of developing treatments for this devastating disorder.
National Institute of Neurological Disorders and Stroke (NINDS) Director Story Landis, in her remarks opening the conference, said there is a "palpable sense of energy, excitement, and enthusiasm" over the scientific progress made since the FRDA gene was discovered 10 years ago. Nearly 150 leading Friedreich's ataxia scientists from around the world discussed their new insights and findings during four days of meetings at the NIH, November 9-12. The public-private partnership underlying this progress and highlighted by the conference involved the NIH, patient advocacy foundations, pharmaceutical and biotechnology industry representatives, and the scientists from academic institutions.
The government sponsors of the conference were the NIH Office of Rare Diseases (NIH/ORD) and NINDS. NIH/ORD was represented at the conference by Dr. Giovanna Spinella. NINDS was represented by its Director and a number of NINDS scientists long involved in advancing the therapeutic approaches examined during this meeting.
Joining FARA at the conference were representatives from many of the foundations with which FARA is collaborating to support the research. These groups included the Muscular Dystrophy Association (MDA), GoFAR (an Italian FA advocacy and research group), Ataxia UK, the National Ataxia Foundation (NAF), the Friedreich's Ataxia Research Association of Australia/New Zealand, the Spanish Ataxia Federation (FEDAES), and EuroAtaxia. Many of these representatives are participants in web-based communications networks such as the Friedreich's Ataxia Parents Group (FAPG) and the International Network of Ataxia Friends (INTERNAF).
Representatives of six pharmaceutical and biotechnology companies also participated. Some of these companies are already involved in advancing promising drug compounds into clinical trials, while others are eager to help take newer discoveries through drug development and into subsequent clinical trials.
FARA has always been convinced that rapid, significant progress in Friedreich's ataxia research requires effective public-private partnership. This conference certainly confirmed that such a partnership has fueled tremendous progress to date and is clearly pointing the way to treatments.
Conference Research Highlights
The conference culminated in a review of the clinical trials currently being prepared and the clinical tests being refined to measure the therapeutic effects in these trials. The compounds currently involved in clinical trials and those for which clinical trials are in late stages of preparation include those outlined below.
Idebenone's Promising Trial Results
At the conference, NINDS clinical researchers reported on the phase II drug trial of idebenone they recently concluded. These investigators concluded that Idebenone appears to be safe and well tolerated and shows "dose-dependent effects on neurological outcome measures" suggesting it has possible therapeutic value in treating Friedreich's ataxia. This six-month, double-blind, placebo-controlled trial involved 48 Friedreich's patients between 9 and 18 years of age who were given idebenone three times a day at fixed daily doses of zero, 5, 15 or 45 milligrams per kilogram of body weight.
The mitochondria-targeted antioxidant MitoQ (Mito Quinone) is being evaluated as a possible treatment for Friedreich's ataxia. Researchers announced they have conducted a phase I clinical trial in healthy subjects and hope to begin a phase II trial in Friedreich's ataxia patients in 2007.
EPI-A0001 Moving Forward
The Food and Drug Administration (FDA) has granted orphan drug status for mitochondrial dysfunction disorders to a compound referred to as EPI-A0001, which targets electron shuttling and energy production in the mitochondria. In July, The NIH accepted EPI-A0001 into the RAID (Rapid Access to Intervention Development) program. This RAID project is intended to move EPI-A0001 from drug discovery through drug development and into clinical trial rapidly as a possible treatment for mitochondrial disorders such as Friedreich's ataxia.
HDAC Inhibitors Increase Frataxin Production
Research in cells and mice indicates that Histone Deacetylase (HDAC) inhibitors have potential for therapeutic increases in frataxin protein production, suggesting they could provide a way of slowing or stopping progression of the disease. Particular HDAC inhibitors have increased frataxin protein production in affected cells and mice to levels equal to or greater than in carrier siblings. These ongoing studies also have not revealed any toxicity. If the results of these studies remain positive, the HDAC inhibitors could enter human trials as a Friedreich's ataxia treatment over the next year or so.
EPO in Early Studies
Human erythropoietin (EPO) is also being studied as a way to raise levels of available frataxin protein in Friedreich's patients. European scientists discovered last year that EPO can raise the frataxin levels in cells from patients. These scientists recently completed a small, 8-week, proof-of-principle trial with about a dozen patients in most of whom frataxin protein levels appeared to be elevated. Discussions are underway as to how best to advance EPO into full-scale clinical trials.
Iron Chelators are Targeted
It has long been known that iron accumulates in the mitochondria of Friedreich's patients. Scientists in several laboratories are investigating a number of molecules intended to remove such excess iron from mitochondria without depleting the rest of the cell of the iron needed for such important functions as making blood and the iron-sulfur clusters required in mitochondrial production of energy with minimum oxidative stress. If this iron-chelation work continues to progress, clinical trials of such compounds could be anticipated next year.
Progress in Understanding Disease Mechanisms and the Importance of Biomarkers
In growing recognition of the importance of understanding the biochemical changes that correlate to progression and treatment of Friedreich's ataxia, participants examined various approaches to identifying and measuring such biomarkers. These biomarkers will be powerful tools, especially in screening potential new drugs, identifying patients who respond to therapeutic drugs, and significantly accelerating the pace of clinical trials by determining the effectiveness of drugs very early in clinical trials. Researchers also emphasized how potentially important these same biomarkers, and a number of the drug compounds being developed for Friedreich's ataxia, will be in advancing treatment options for a number of other, related diseases such as Parkinson's Disease, Huntington's Disease, Alzheimer's Disease, ALS, stroke, diabetes and Spinal Muscular Atrophy.
FARA President Ron Bartek pointed to the clinical trials being planned around the world as the vanguards of the treatment era for Friedreich's ataxia and a range of related disorders. "FARA is especially grateful for the public-private partnerships that have pulled together the collaborative forces of such excellent and dedicated teams from government, industry, charitable foundations, and the scientists around the world. We are all working hard together to attack this disease on many fronts and are confident we will soon have effective treatments that will slow, stop and reverse the damage caused by this disease."
FARA will publish abstracts from the conference on its website and more detailed reports of the scientific progress in FARA's upcoming newsletter.
About Friedreich's Ataxia
About one of every 50,000 people in the United States has Friedreich's ataxia, which is caused by a genetic defect that prevents adequate production of the protein frataxin — essential for proper functioning of mitochondria, the energy producers for cells. Specific symptoms, which typically appear first between the ages of five and 15, include loss of strength and coordination in hands, arms and legs, slurred speech, reduced vision and hearing, scoliosis, heart disease, and diabetes. Friedreich's ataxia usually leads to full-time wheelchair use by about the age of twenty and death in early adulthood. There is currently no treatment or cure.
FARA is a national, public, 501(c)(3), non-profit, tax-exempt organization dedicated to the pursuit of scientific research leading to treatments and a cure for Friedreich's ataxia. FARA's mission is to slow, stop, and reverse the damage caused by this disorder.
President, Friedreich’s Ataxia Research Alliance