Validation of small molecule therapeutic leads for treatment of MPS I disease

Mucopolysaccharidosis I (MPS I) is a serious genetic disease that leads to early death. In this disease, there is a single enzyme that is missing or deficient, an enzyme that resides in human cells in special organelles (lysosomes). Enzyme replacement therapy is the conventional treatment but the associated drug is very costly (up to one million dollars per patient per year). Furthermore the treatment is not effective for disease processes in the brain and skeleton, partly because the supplied enzyme cannot gain access to these tissues. Another type of therapy is enzyme enhancement therapy. This uses a small molecule that assists the otherwise defective lysosomal enzyme to adopt the correct shape. The result is enhanced enzymatic activity – the enzyme achieves its correctly folded conformation and can now transit inside the human cell to arrive at its normal locale where it can function, the lysosome. We recently identified a drug candidate that would be less costly, allow for oral delivery, and has well-known properties. We will evaluate this molecule for its therapeutic value in the treatment of MPS I disease. We will further determine how this small molecule and related compounds work to rescue defective enzymes and thus act as therapeutics.

– Dr. Allison R. Kermode, Professor

Simon Fraser University Burnaby, BC Canada