title: Drug development for rare mitochondrial disorders.
abstract: Currently, all treatment of mitochondrial disorders is performed with dietary supplements or by off-label use of drugs approved for other indications. The present challenge is translation of our collective knowledge of the molecular details underlying the pathophysiology of mitochondrial disorders into safe and effective therapies that are approved by the regulatory authorities. Molecular details permit precise diagnoses, but homogeneity is gained at the expense of limiting numbers of subjects for clinical trials and of small markets from which to recoup the considerable expense of drug discovery and development. The Food and Drug Administration recognizes that trial designs suitable for common diseases are often not feasible for rare disorders. They have developed a number of programs to facilitate development of novel therapies for such rare diseases, without compromise of regulatory standards. With advances in technology, including the use of biomarkers, replacement therapies and sophisticated trial designs, both biotechnology firms and, increasingly, large integrated pharmaceutical companies, are taking advantage of the opportunities in rare disorders. Precise molecular delineation of pathophysiology and of responsive patients has led to success rates with rare diseases that are significantly greater than those for common disorders. It appears likely, but not yet proven, that this may now be the case for rare mitochondrial disorders as well.
authors: Clinical Translational Medicine, 19 Sugar Knoll Drive, Suite 203, Devon, PA 19333-1558, USA. hurko@ctmclinical.com
authors: Orest
authors: O
authors: Hurko
mesh_terms: D015415:Biomarkers; D019587:Dietary Supplements; D017277:Drug Approval; D006801:Humans; D007880:Legislation, Drug; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy*; D056687:Off-Label Use; D009965:Orphan Drug Production; D035583:Rare Diseases / Q000188:drug therapy*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015415:Biomarkers