Hurler Syndrome (MPS I)

Hurler Syndrome is one of a family of lysosomal storage diseases called mucopolysaccharidoses (MPS). These are inherited diseases caused by a defect in one of the genes needed to break down glycosaminoglycans – long chain sugars. These glycosaminoglycans accumulate in the body’s cells and in connective tissues, significantly affecting the eyes, heart, brain, and bone structure. In Hurler Syndrome, children stop developing between the ages of 2 and 4, with a progressive mental decline and loss of physical skills. Affected children usually die before age 10 of respiratory or cardiac complications.

Status

Current therapies for Hurler Syndrome are enzyme replacement therapy, in which the purified enzyme is regularly infused intravenously into patients, and bone marrow transplantation, in which the transplanted cells provide the missing enzyme. Both of these therapies are most effective when performed immediately after diagnosis, before organ damage has become severe. Bone marrow transplantation has significant side effects, some due to the need for anti-rejection drugs, and others from the transplant itself, such as graft-vs.-host disease. Enzyme replacement therapy can relieve some symptoms, but typically is not effective in preventing mental decline.

Gene therapy for Hurler Syndrome involves delivering a normal copy of the glucocerebrosidase gene to the liver, allowing the liver to secrete enough enzyme to ameliorate symptoms without the need for repetitive infusion. ReGenX’s AAV8 serotype is significantly more efficient in delivering genes to the liver than other serotypes such as AAV2, and more efficient than other gene therapy delivery systems such as lentivirus. The proposed therapeutic is in the research stage of development.

Market

Hurler Syndrome is a rare disease affecting approximately 1 in 115,000 individuals. There is an estimate in the United States that 1 in 25,000 births will result in some form of MPS.¹ There is no cure for Hurler Syndrome, and costs for treatment are estimated to be $435,000 annually.²