Mitochondrial Disease: Clinics, Genetics, Mechanism &Therapy (GENOMIT)

Mitochondria are the power plants of the cell. The produced energy is saved as so called ATP, which is formed via the breakdown of carbohydrates, fatty acids and proteins. In the last few years a plethora of new genetic defects was identified in patients with mitochondrial disorders (mitochondriopathy). Till now defects in about 250 genes were described. It can be assumed that one tenth of all human genes are associated with mitochondrial disorders. Every disease has a unique genetic background and in general no effective therapies are available. GENOMIT is a network of eight partners in Germany, Austria, Italy, France, and USA which act in close collaboration with the International Mitochondrial Patient (IMP, http://www.mitopatients.org/) organization to improve the diagnosis and care of mitochondrial disease patients. GENOMIT will i) create the largest mitochondrial patient database worldwide, integrating four existing national registries from Europe and USA, including more than 4500 patients, ii) boost genome-wide diagnostics and optimize interpretation of genomic data by aggregating an enormous number of datasets, iii) extend functional studies on novel genes and pathways involved in the pathophysiology of mitochondriopathies, and iv) evaluate novel therapeutic options for example the so called protein replacement therapy with particular emphasis on defects of the respiratory chain complex I, that is frequently affected. GENOMIT partners are established national hubs for the biochemical and genetic diagnosis and care of patients with mitochondriopathies. They represent the existing national patient registries and have access to the largest collection of mitochondriopathy-related genetic data in Europe. Each of them has also developed unique expertise that will be shared synergistically within the network. GENOMIT will thus create the critical mass to expand knowledge on the natural history, and the connection of genetic defects and the physiological manifestation of mitochondrial disease, and gain insight into pathophysiologic mechanisms and feasibility of novel therapeutic approaches. The main task of the Austrian subproject is the functional characterization of novel genes and signalling pathways involved in the pathology of mitochondrial diseases (point iii above). Furthermore, we participate in the other three work packages. During the previous E-rare project (I 920-B13, Mitochondriopathies Network for diagnosis and therapy [GENOMIT]) the Salzburg team was involved in the identification of four novel genetic defects. In total 19 scientific articles were published.