Raymond Wang, MD, Metabolic Specialist and Director of the Multidisciplinary Lysosomal Storage Disorder Program at Children’s Hospital of Orange County, provides an extensive overview of mucopolysaccharidosis type I (MPS I), also known as Hurler syndrome. In this interview, Dr. Wang explains this rare condition, including its pathophysiology, prevalence, and natural progression. He also discusses the current treatment options for MPS I as well as the work he is doing to assess the safety and efficacy of gene therapy (RGX-111) for this rare disease.
MPS I is an inherited lysosomal storage disorder caused by a deficiency in the enzyme, alpha-L-iduronidase, which is responsible for breaking down glycosaminoglycans (GAGs). In moderate to severe forms of the disease, the accumulation of GAGs in the central nervous system leads to hydrocephalus, spinal cord compression, and cognitive impairment. Additional symptoms may include clouded corneas; enlarged liver, spleen, and heart; noisy breathing; recurring upper respiratory tract; ear infections; difficulty swallowing; and periodic bowel problems.
Currently, there are two main treatment options for MPS I – enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). ERT involves intravenous iduronidase which is a life-long treatment usually given every week. Unfortunately, intravenous iduronidase cannot pass the blood-brain barrier which makes it ineffective in treating neurological symptoms associated with severe MPS I. HSCT is effective in treating neurological symptoms; however, this therapy requires the patient to undergo chemotherapy to eliminate their own stem cells before receiving the foreign, healthy stem cells. In addition, graft-versus-host disease is a concern with HSCT. As both of these treatment options have significant disadvantages, there has been a push for companies to develop a gene therapy for MPS I, which, if successful, would be curative.
RGX-111 is a recombinant adeno-associated virus serotype 9 capsid containing a human IDUA expression cassette (AAV9.CB7.hIDUA). When administered to the central nervous system (CNS), RGX-111 may provide a permanent CNS source of secreted alpha-L-iduronidase, potentially preventing the progression of cognitive deficits that otherwise occurs in MPS I patients.
To learn more about MPS I and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/