GTX-102: Antisense Oligonucleotide for Angelman Syndrome (AS)

AS: a debilitating, rare, neurogenetic disorder that primarily affects the nervous system

AS is caused by loss-of-function of the maternally inherited allele of the UBE3A gene. In all people, the paternally inherited allele of the UBE3A gene is naturally silenced by the UBE3A antisense transcript (UBE3A-AS). Therefore, patients with AS have limited or no UBE3A protein expression and experience developmental delay, balance issues, motor impairment, anxiety, disturbed sleep and debilitating seizures. Some individuals with AS are unable to walk and most do not speak. No therapies are approved for AS, which affects an estimated 60,000 people in the developed world.

Evaluating GTX-102 to reactivate expression of the UBE3A gene in patients with AS

GTX-102 is an investigational antisense oligonucleotide (ASO) therapy designed to inhibit expression of UBE3A-AS in order to prevent silencing of the paternally inherited allele of the UBE3A gene and reactivate expression of the deficient protein. GTX-102 is delivered as an intrathecal infusion. A Phase 1/2 study evaluating the tolerability and safety of GTX-102 and its effect on all major domains of the AS in pediatric patients is currently ongoing in the U.S., U.K. and Canada. Preliminary data showed that all five initial patients had increases of “much improved” or better in the global score of the Clinical Global Impressions-Improvement-Angelman Syndrome (CGI-I-AS) endpoint, including improvements across all individual domains. Other measures of AS also improved. A Grade 1 or 2 serious adverse event of lower extremity weakness was observed in all five patients consistent with local contact inflammation due to GTX-102 intrathecal delivery.

GTX-102 was granted Orphan Drug Designation, Rare Pediatric Disease Designation and Fast Track Designation in the United States.

GTX-102 is being developed in partnership with GeneTx Biotherapeutics LLC. Ultragenyx has an exclusive option to acquire GeneTx.

Learn more about GTX-102 clinical studies