GTX-102: Antisense oligonucleotide for the potential treatment of Angelman syndrome (AS)
Stage: Phase 1/2
Disease: Angelman syndrome
Prevalence: 60,000 in our territories
Disease Mechanism: Loss-of-function or deletion of the maternally inherited allele of the UBE3A gene
Symptoms: Developmental delay, communication impairments, balance issues, motor impairment, anxiety, disturbed sleep, seizures
Treatment Modality: Antisense oligonucleotide
Treatment Mechanism: Inhibit expression of the paternal UBE3A antisense
AS: lack of UBE3A protein impairs neurodevelopment
AS is caused by loss-of-function or deletion of the maternally inherited allele of the UBE3A gene. In all people, the paternally inherited allele of the UBE3A gene is naturally silenced in the neurons of the brain and spinal cord by the UBE3A antisense transcript (UBE3A-AS). Therefore, individuals with AS have limited or no UBE3A protein expression in the central nervous system and experience developmental delay, communication impairments, 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 our territories.
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-ATS 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 AS in pediatric patients is currently ongoing in the U.S., U.K. and Canada.
GTX-102 was granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation in the United States.