Angelman Syndrome (AS) is a rare neurogenetic disorder that affects approximately 1 in 15,000 births worldwide. It is characterized by developmental delay, lack of verbal speech, seizures, sleep disorders, and motor impairments. Despite its significant impact on individuals and their families, there is currently no approved therapy for Angelman Syndrome. However, a groundbreaking collaboration between the Foundation for Angelman Syndrome Therapeutics (FAST) and the University of Pennsylvania is offering new hope for patients through the development of an investigational adeno-associated virus (AAV) gene therapy for Angelman Syndrome.
Image Source: Dreamstime
Understanding Angelman Syndrome
Angelman Syndrome is a nondegenerative neurogenetic disorder that causes a range of physical, cognitive, and behavioral impairments. It is typically caused by a deletion or mutation of the UBE3A gene on chromosome 15. This gene is responsible for producing a protein called ubiquitin protein ligase E3A (UBE3A), which plays a crucial role in brain development and function.
Individuals with AS experience delays in reaching developmental milestones, such as sitting, crawling, and walking. They also have severe speech impairments or are completely nonverbal. Additionally, AS is associated with seizures, sleep disorders, and motor difficulties, further impacting the quality of life for affected individuals and their families.
The Promise of AAV Gene Therapy
The collaborative efforts between FAST and the University of Pennsylvania have paved the way for a potential breakthrough in Angelman Syndrome treatment. The focus of this partnership is the development of an investigational adeno-associated virus (AAV) gene therapy specifically designed to address the underlying genetic cause of Angelman Syndrome.
AAV gene therapy involves the delivery of a functional copy of the UBE3A gene into the central nervous system (CNS) using a modified adeno-associated virus as a vehicle. By introducing a functional UBE3A gene, the therapy aims to restore the production of the UBE3A protein in the brain, potentially alleviating the symptoms associated with AS.
Preclinical Research and Promising Results
Since 2017, FAST has been sponsoring preclinical research studies at the University of Pennsylvania’s Gene Therapy Program. The objective of these studies is to gather robust preclinical data to support the further advancement of the AAV gene therapy for Angelman Syndrome.
The preclinical data obtained so far has been highly promising, indicating the potential efficacy and safety of the AAV gene therapy. These positive results have been instrumental in reaching a critical inflection point, allowing for the selection of a promising human clinical candidate for further advancement.
The Importance of Excellent Science
FAST’s commitment to advancing excellent science in the pursuit of therapies for Angelman Syndrome is unwavering. In a world where priorities may shift, FAST remains steadfast in its mission to prioritize the needs of individuals living with AS.
According to Allyson Berent, DVM, DACVIM, Chief Science Officer of FAST, “To see the promising results of this robust preclinical data package, based on research that FAST has been so diligently funding for years, is incredibly gratifying. It is our job to ensure that excellent science is always advanced as safely and efficiently as possible, and that we seize every opportunity to potentially benefit those living with Angelman Syndrome.”
The Role of the University of Pennsylvania
The University of Pennsylvania’s Gene Therapy Program (GTP) and the Orphan Disease Center have played a pivotal role in the efforts to develop the AAV gene therapy for AS. Under the leadership of Jim Wilson, MD, PhD, the GTP has been at the forefront of gene therapy research and development.
Dr. Wilson emphasizes the productive and rewarding nature of the collaboration with FAST and the entire Angelman Syndrome community. He states, “Our two teams have been both mission and data driven, working closely together to reach this critical inflection point, and FAST and GTP have made an instrumental decision on a promising human clinical candidate to further advance this gene therapy forward quickly and safely for the potential treatment of Angelman Syndrome.”
Looking Ahead: Clinical Trials and Hope for the Future
The collaborative research and development agreement between FAST and the University of Pennsylvania marks a significant milestone in the journey towards finding a treatment for Angelman Syndrome. The promising preclinical data package has laid the foundation for the next phase: IND-enabling studies and subsequent first-in-human clinical trials.
As the AAV gene therapy for AS progresses through these stages, there is hope that it will prove to be a safe and effective treatment option for individuals living with this disorder. The potential impact of this therapy on the lives of patients and their families is immeasurable, offering a glimmer of hope in a previously unmet clinical need.
For more information on Angelman Syndrome and other neurological diseases, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/