Dr. Murray Potter
Brain Targeted MPS II therapy delivered microencapsulated cells
MPS II, or Hunter syndrome, is an inherited disorder affecting males caused by deficiency of the enzyme iduronate sulfatase. This deficiency causes bone abnormalities, organ enlargement, brain deterioration and early death. It is now possible to treat many features of MPS II by weekly injections of a purified form of the missing enzyme (enzyme replacement therapy, ERT). Unfortunately, the brain remains difficult to treat. We are developing a new treatment that targets the brain by modifying the replacement enzyme so that it can better reach the brain. The modification involves adding a targeting signal called “TAT” to the enzyme. TAT has been successfully shown to deliver other proteins and enzymes to the brain in animal experiments.
Instead of directly injecting the modified enzyme, we will transplant cells that can produce the enzyme. Transplantation removes one of the drawbacks of ERT, which is the need for weekly injections. The cells will be placed inside a special microcapsule to protect them from rejection, allowing one transplantation procedure to last for months or years. Microencapsulated cells have already successfully been used in animal experiments, including treatment of MPS II mice.
We feel that this research will bring a treatment for the brain disease in MPS II and related disorders closer to reality. This goal is directly related to one of the underlying purposes of the Canadian MPS Society, that of finding a cure for all MPS.
Dr. Lorne Clarke
Serum Biomarker for MPS
The mucopolysaccharidoses (MPSs) represent a group of complex progressive multi-system diseases which are caused by metabolic defects in the degradation of glycosaminoglycans (GAGs). The recent introduction of enzyme replacement (ERT) regimes for MPS I and MPS II has brought to light the importance of developing objective methods to evaluate patients. The clinical heterogeneity manifest as variable age of onset as well as variable rates of disease progression, clearly complicate the ability of physicians to accurately prognosticate clinical course for individual patients and leads to significant difficulty in objectively evaluating the effectiveness of treatment regimes. The development of biomarkers that reflect disease severity, disease progression and responsiveness to treatment regimes will be an invaluable tool.
My laboratory has identified a potential serum biomarker for the MPSs and propose in this grant application to develop a sensitive and specific ELISA based assay for this biomarker.
