SARASOTA, Fla., Feb. 14, 2020 /PRNewswire/ -- GeneTx Biotherapeutics LLC today announced that it has received IRB approval from Rush University Medical Center in Chicago, IL to begin the "KIK-AS" (Knockdown of UBE3A-antisense in Kids with Angelman Syndrome) Phase 1/2 clinical study of GTX-102, an experimental antisense oligonucleotide being evaluated for the treatment of Angelman syndrome (AS).
The objective of this Phase 1/2 open-label, multiple-dose, dose-escalating study is to evaluate the safety, tolerability, and plasma and cerebrospinal fluid (CSF) concentrations of GTX-102 in pediatric patients with Angelman syndrome. Approximately 20 patients (male and female) ≥ 4 and ≤ 17 years of age with a genetically confirmed diagnosis of full maternal UBE3A gene deletion will be enrolled. Further details can be referenced at: https://clinicaltrials.gov/ct2/show/NCT04259281.
"A tremendous amount of basic research over decades, and intense research and development over the last couple of years has now brought us to the cusp of testing a novel drug in individuals with Angelman syndrome," stated Scott Stromatt, M.D., Chief Medical Officer of GeneTx Biotherapeutics. "This is truly an exciting time for patients, families, and medicine."
"The GeneTx team continues to make significant progress in advancing the GTX-102 program for patients with Angelman Syndrome, and we look forward to continuing our work with the team to move this program into the clinic," said Camille L. Bedrosian, M.D., Chief Medical Officer of Ultragenyx Pharmaceutical, a biopharmaceutical company that has partnered with GeneTx to develop GeneTx's GTX-102.
Rush University Medical Center in Chicago will be the first center to enroll patients with additional sites planned for Boston, Cincinnati, Denver, Los Angeles, New York and Ottawa, Canada. “We are extremely excited to begin the process of understanding the effects of GTX-102, which is directed at correcting the genetic defect and potentially improving the quality of life of our patients with Angelman syndrome,” said Elizabeth Berry-Kravis MD PhD, PI of the Rush University site, and co-director of the Angelman Syndrome Clinic at Rush.
About Angelman Syndrome
Angelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. The maternal-specific inheritance pattern of Angelman syndrome is due to genomic imprinting of UBE3A in neurons of the central nervous system, a naturally occurring phenomenon in which the maternal UBE3A allele is expressed and the paternal UBE3A is not. Silencing of the paternal UBE3A allele is regulated by the UBE3A antisense transcript (UBE3A-AS), the intended target of GTX-102. In almost all cases of Angelman syndrome, the maternal UBE3A allele is either missing or mutated, resulting in limited to no protein expression. This condition is typically not inherited but instead occurs spontaneously.
Individuals with Angelman syndrome have developmental delay, balance issues, motor impairment, and debilitating seizures. Some individuals with Angelman syndrome are unable to walk and most do not speak. Anxiety and disturbed sleep can be serious challenges in individuals with Angelman syndrome. While individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently. Angelman syndrome is not a degenerative disorder, but the loss of the UBE3A protein expression in neurons results in abnormal communications between neurons. Angelman syndrome is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome; however, several symptoms of this disorder can be reversed in adult animal models of Angelman syndrome suggesting that improvement of symptoms can potentially be achieved at any age.
GTX-102 is an investigational antisense oligonucleotide designed to target and inhibit expression of UBE3A-AS. Nonclinical studies show that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS. Reactivation of paternal UBE3A expression in animal models of Angelman syndrome has been associated with improvements in some of the neurological symptoms associated with the condition. GTX-102 has been granted Orphan Drug Designation and Rare Pediatric Disease Designation from the U.S. Food and Drug Administration (FDA). In August 2019, GeneTx and Ultragenyx announced a partnership to develop GTX-102, with Ultragenyx receiving an exclusive option to acquire GeneTx.
About GeneTx Biotherapeutics
GeneTx Biotherapeutics LLC is a startup biotechnology company singularly focused on developing and commercializing a safe and effective antisense therapeutic for the treatment of Angelman syndrome. GeneTx was launched by FAST, a patient advocacy organization and the largest non-governmental funder of Angelman syndrome research. GeneTx licensed the rights to antisense technology intellectual property from The Texas A&M University System in December 2017.