Raymond Wang, MD, Metabolic Specialist at Children’s Hospital of Orange County, gives an update on children with for mucopolysaccharidosis type I (MPS I) given gene therapy.

 MPS I is a lysosomal 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 symptoms that can include clouded corneas; enlarged liver, spleen, and heart; noisy breathing; recurring upper respiratory tract; ear infections; difficulty swallowing; and periodic bowel problems. In moderate to severe forms of the disease, GAGs accumulation can impact the central nervous system dramatically (developmental delay, cognitive impairment, etc). 

There are two treatment options for individuals with MPS I – enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). ERT involves weekly intravenous iduronidase infusions. Unfortunately, intravenous iduronidase does not pass through the blood-brain barrier. In contrast, 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. Graft-versus-host disease is also a concern with HSCT.

RGX-111 is a  recombinant adeno-associated virus serotype 9 (AAV9) capsid containing a human alpha-L-iduronidase expression cassette in development to treat the central aspects of MPS I.  As Dr. Wang states, he is involved in an ongoing phase 1/2, first-in-human, multicenter, open-label, dose escalation trial (NCT03580083), in children with severe MPS I given RGX-111 injection to the CNS with 104 week follow-up for safety, tolerability, and efficacy. 

Data  from five of the nine patients was presented at WORLDSymposium by Dr. Wang. Of those five children, four children showed significant reduction in CSF GAGs levels. More importantly, all five children were within normal range of development.  In comparison, most MPS I children without treatment would start to show a decline in development during the same time frame (approximately 2 years).

Regarding safety, Dr. Wang noted no adverse events were observed but he cautioned that for this therapy, children are put on immunosuppressant therapy for approximately one year.

To learn more about MPS I and other rare lysosomal disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/