Gene Therapy Developments

UX111 (Ultragenyx Pharmaceutical)

For children with Sanfilippo Syndrome Type A (MPS IIIA), a crucial enzyme is missing that may lead to a toxic buildup in the brain. MPS IIIA is a fatal condition with no approved treatment that affects the central nervous system. The changes in the copies of the SGSH gene can lead to a lack of the sulfamidase enzyme needed to break down a type of complex sugar called heparan sulfate. When heparan sulfate builds up in the body’s cells, it can cause rapid neurodegeneration with onset in early childhood. About 3,000 to 5,000 patients in commercially accessible geographies have been affected, with a median life expectancy of 15 years.

The AAV9-based gene therapy targets Sanfilippo syndrome type A. Clinical trial data indicate that UX111 can slow or halt neurodegeneration, preserving cognitive and motor functions in children. Ultragenyx is seeking accelerated FDA approval, with cerebral spinal fluid heparan sulfate accepted as a surrogate endpoint for efficacy evaluation.

EGT-101 Gene Therapy (Esteve)

The EGT-101 is a groundbreaking first-in-class AAV-9 gene therapy. Aside from gaining scientific attention, Esteve has received significant financial backing through grants from Spain’s Ministry of Economy and Competitiveness and the Ministry of Health, Social Policy and Equality. Such recognition underscores the scientific community’s belief in its potential and the urgent need for therapy for Sanfilippo Syndrome.

A healthy, working gene is delivered directly into the cerebrospinal fluid (the fluid surrounding the brain and spinal cord) via a one-time intracerebroventricular injection. This treatment targets Sanfilippo Syndrome type A (MPS IIIA). This precise approach aims to address the core genetic error in Sanfilippo Type A, allowing the body to produce the missing enzyme and potentially halt or reverse the devastating progression of the disease.