Mitochondrial Diseases, Treatments, and FDA Orphan Legislation

Abstract

Mitochondria originated during a key endosymbiotic event, when an enveloped bacterium or invasive parasite adjusted to its intracellular surroundings and formed the first eukaryotic cell. The symbiote evolved into a specialist organelle supplying the vast majority of a cell's ATP energy supply as well as regulation of cellular differentiation, cell death, the cell cycle, and cell growth. Due to its double layered membranes and separate DNA control systems, it has proved an elusive target for medicines, and is responsible for a host of diseases and may be a key contributor to the aging process. Mitochondrial disorders, though a diverse family ranging from cardiac diseases to a subset of Parkinson's syndrome, individually affect relatively small populations and may therefore fall under the purview of the Orphan Drug legislation enforced by the Food and Drug Administration. While no viable delivery mechanism for macromolecules larger than proteins currently exists for the inner mitochondrial matrix, several academic research papers suggest that the unique morphological challenges of mitochondria may be overcome. A survey of these approaches is presented within the context of mitochondrial structure, and a path towards economical drug development via the Orphan Drug system is proposed