Raymond Wang, MD, Metabolic Specialist and Director of the Multidisciplinary Lysosomal Storage Disorder Program at Children’s Hospital of Orange County, gives an overview of the treatment landscape for mucopolysaccharidosis type I (MPS I).
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). These GAGs accumulate in the tissues of MPS I patients, resulting in a diverse clinical profile. In moderate to severe forms of the disease, this accumulation 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.
As Dr. Wang explains, there are two MPS I treatment options that are approved or recognized as efficacious – 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. Additionally, patients usually run out of veins to inject and may require a central venous catheter which can become infected. HSCT, in comparison, 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.
To learn more about MPS I and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
