Scheme: Wolfson Research Merit Awards
Organisation: University of Oxford
Dates: Aug 2013-Jul 2018
Summary: We are interested in a group of rare genetic diseases called lysosomal storage diseases. About 70 of these inherited disorders are known and they occur in the general population with a combined frequency of 1:5000 live births. Most have a neurodegenerative clinical course and typically affect infants and children. The vast majority of these diseases are without effective therapies. We previously developed a small molecule treatment (a drug called miglustat) that is currently prescribed to patients with two of these diseases, Gaucher disease and Niemann-Pick type C (NPC) disease. We have recently developed a major interest in NPC disease as by understanding this disease it tells us a lot about how normal cells work and in particular how the lysosome, the cells waste disposal and recycling centre functions. In addition, we have found that inflammation is altered in this disease and a significant number of NPC patients develop an inflammatory disease of the bowel called Crohn's disease. By studying this rare genetic disease we are therefore gaining knowledge about the causes of more common diseases with a view to generating new therapeutics for treating both rare and common diseases. This year we have found that treatments we have developed for rare NPC disease help clear pathogenic mycobacteria in Zebra fish validating this therapeutic approach.
We have also identified two novel pathways defective in NPC disease and are studying the underlying mechanisms resulting in deficiency of these aspects of cell function.