Raymond Wang, MD, Metabolic Specialist and Director of the Multidisciplinary Lysosomal Storage Disorder Program at Children's Hospital of Orange County, discusses RGX-111, an investigational gene therapy for mucopolysaccharidosis type I (MPS I). Data from this study was recently presented at WORLDSymposium 2022.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 glycosaminoglycans, spinal cord compression, and cognitive impairment. 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. In this phase 1/2, first-in-human, multicenter, open-label, dose escalation trial, participants CNS involvement or severe MPS I, four months of age or older, received one image-guided RGX-111 injection to the CNS with 104 week follow-up for safety, tolerability, and efficacy. Assessments include cerebrospinal fluid, plasma, and urine biomarkers; cognitive, language, and motor neurodevelopmental scales; and imaging. Two subjects have been dosed at Dose 1 (1.0 x 1010 genome copies/g brain mass) and 3 subjects have currently been dosed at Dose 2 (5.0 x 1010 genome copies/g brain mass). Enrollment for Dose 2 continues.