The lysosome is the recycling center of the cell and when dysfunctional causes severe human disease. We have had a long-term interest in understanding and treating lysosomal storage diseases, a group of inherited metabolic diseases typically characterized by severe pathology in the brain. They occur at a collective frequency of 1:5000 and typically present in infancy or childhood but adult-onset variants also occur. They are caused my inherited mutations in genes that encode lysosomal enzymes. membrane or soluble proteins.
The majority of these diseases lack specific disease modifying therapies. We have been studying a subgroup of these disorders for many years, the glycosphingolipid storage disorders, that includes Gaucher, Fabry, Tay-Sachs, Sandhoff and GM1 gangliosidosis. In addition, we have a major interest in Niemann-Pick type C disease, which involves the secondary storage of glycosphingolipids. The underlying disease mechanisms remain incompletely understood and new therapies are urgently needed.
We were involved in the pre-clinical development of the substrate reduction therapy drug miglustat that is now approved world-wide for type 1 Gaucher disease and more recently in Europe for treating Niemann-Pick type C.
Our current interests are in four areas:
• Lysosomal storage disorders, pathogenesis and therapy
• The effects of lysosomal storage on the immune system
• Development of biomarkers for monitoring storage disease patients