Molecular basis for inherited mitochondrial disease
Mitochondrial diseases are genetic conditions affecting around 1 in 5,000 of the population of the UK. Since mitochondria are key players in the metabolism of energy, mitochondrial disorders mostly affect the organs of the body that require a great deal of energy, such as the nervous system, the heart and skeletal muscle. These disorders therefore result in severe disability and significantly reduced lifespan. However, mitochondrial diseases can present with a wide variety of symptoms, making the task of identifying the underlying causes correspondingly harder. As a consequence, it is extremely difficult to treat mitochondrial disease, or even to identify a suitable therapeutic approach.
Using new high-throughput DNA sequencing techniques we are identifying the genes and proteins involved in the group of diseases caused by defects in the mitochondrial energy-supplying (oxidative phosphorylation) pathway . Using the SILAC method of quantitative proteomics in collaboration with the Unit's Mass Spectrometry Facility, we are characterizing the molecular basis of the interactions and function of those we have identified over the last five years. These insights, along with a careful analysis of the pathological and physiological features of the conditions are providing clues that allow us to propose and test novel therapeutic strategies for this currently intractable group of diseases.
There is an urgent need for effective therapies for mitochondrial disease. We are focusing our efforts on two main strategies, resulting from our expanding knowledge of the molecular mechanisms of disease and on the pathways that control mitochondrial homeostasis: (i) activation of mitochondrial biogenesis and (ii) AAV-mediated gene replacement.