Angelman syndrome, a rare genetic condition, has been a central focus of UConn researcher Stormy Chamberlain’s career for over a decade. Since 2009, Chamberlain has been using induced pluripotent stem cells (iPSCs) in her lab at UConn Health to study human imprinting disorders that could lead to a cure.
Through a newly announced exclusive licensing agreement and research collaboration, Chamberlain and fellow UConn School of Medicine researcher Noelle Germain are now working with biopharmaceutical company Ovid Therapeutics Inc. on a promising genetic therapy.
Angelman syndrome affects approximately 1 in 12,000 to 1 in 20,000 people globally, and there are currently no approved therapies. People with Angelman syndrome experience developmental delays, have trouble walking or balancing, and are prone to seizures. They also have limited speech abilities, despite a tendency to laugh, smile, and have a happy demeanor. Individuals with Angelman syndrome typically have normal lifespans but are unable to live independently and require constant care from family or caregivers.
Current treatment options primarily consist of behavioral interventions and pharmacologic management of symptoms. Chamberlain and Ovid hope to provide more options to patients with Angelman through their strategic research collaboration.
Angelman syndrome occurs when a single gene inherited from a mother’s 15th chromosome is deleted or inactive. The paternal copy of that gene, known as ubiquitin protein ligase E3A or UBE3A, is normally silenced in brain cells by UBE3A-antisense, a regulatory RNA.
Through the research collaboration and license agreement, Chamberlain, Germain, and Ovid will work to accelerate the development of a next-generation short hairpin RNA (shRNA)-based therapeutic for Angelman syndrome. An shRNA-based therapeutic may address the underlying genetic cause of Angelman syndrome by reducing the expression of UBE3A-antisense and restoring the function of UBE3A. This genetic approach may be used in combination with OV101 (gaboxadol), Ovid’s novel therapy. OV101 is currently in clinical development for the treatment of Angelman syndrome and Fragile X syndrome. Topline results in Angelman syndrome are expected at the end of 2020.
“An shRNA therapeutic can target the genetic cause of Angelman syndrome at its source and may offer potential advantages to other next-generation approaches,” says Chamberlain. “Ovid is uniquely positioned to accelerate an shRNA therapeutic through late preclinical and clinical development, and our lab looks forward to working with the team at Ovid towards our common objective of impacting the lives of individuals living with Angelman syndrome and their families.”
While Ovid and the UConn research team are hopeful that OV101 will serve as a core therapy for this Angelman syndrome, the collaboration will also grow the research pipeline for the future to ensure new therapies for individuals living with Angelman syndrome.