Rush University Medical Center’s institutional review board was the first to greenlight the GeneTX Biotherapeutics’ Phase I/2 clinical trial of GTX-102, its investigational therapy for the treatment of Angelman syndrome.
What is Angelman Syndrome?
Angelman syndrome is a genetic disorder that mainly affects the nervous system. Symptoms can include a small head and a specific facial appearance, severe intellectual disability, developmental disability, speaking problems, balance and movement problems, seizures and sleep problems. Children usually have a happy personality and have a particular interest in water. It originates from a lack of function of part of chromosome 15 inherited from a person’s mother. Most of the time, it is due to a deletion or mutation of the UBE3A gene from a person’s father and one from their mother. Occasionally, it is due to inheriting two copies of chromosome 15 from a person’s father and none from their mother. As the father’s versions are inactivated by a process known as genomic imprinting, no functional version of the gene remains. It is typically due to a new mutation rather than one inherited from a person’s parents. Diagnosis is based on symptoms and possibly genetic testing. Frequency is 1 in 12,000 to 1 in 20,000.
The objective of the Phase I/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.
What is GTX-102?
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.
Rush University Medical Center in Chicago is the first site to enroll patients with additional sites planned for Boston, Cincinnati, Denver, Los Angeles, New York and Ottawa, Canada.
Elizabeth Berry-Kravis, MD, PhD, PI of the Rush University site and co-director of the Angelman Syndrome Clinic at Rush, reported, “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.
Who is GeneTx Biotherapeutics?
GeneTx Biotherapeutics was set up as a subsidiary of the Foundation for Angelman Syndrome Therapeutics for the development and commercialization of an investigational antisense drug, GTX-102, for the treatment of Angelman syndrome (AS).
Elizabeth Berry-Kravis, MD, PhD, PI