GT-AS for Angelman Syndrome

GT-AS is an investigational gene therapy candidate originally created by Agilis Biotherapeutics to treat Angelman syndrome, a rare genetic disorder characterized by severe intellectual and developmental disability. Agilis Biotherapeutics was acquired by PTC Therapeutics in 2018. PTC Therapeutics is now continuing the development of GT-AS.

This potential gene therapy has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) and orphan medicinal product status by the European Commission (EC).

What is Angelman syndrome?

Angelman syndrome is caused by a mutation in the UBE3A gene, which encodes an enzyme called E6-AP. This enzyme is critical for the function of the central nervous system. It is a type of enzyme called a ubiquitin ligase. It attaches a small molecule called ubiquitin to proteins to mark them for degradation by the cell.

A balance exists between protein synthesis and protein degradation within every cell. Without the E6-AP enzyme, that balance is disrupted, which can be especially problematic during development.

How does GT-AS work?

GT-AS uses a virus that has been modified so it does not cause disease — called an adeno-associated virus (AAV) — as a carrier. The AAV delivers a normal copy of the UBE3A gene to specific central nervous system cells with the aim of restoring the production of the E6-AP enzyme. This process is designed to improve cell function and rescue neurological defects in Angelman syndrome.

GT-AS research

In a study with Angelman syndrome mouse models, researchers directly injected an AAV vector carrying the UBE3A gene into the brain of the animals. This restored local UBE3A gene activity, increased levels of E6-AP enzyme, and improved the cognitive deficits associated with Angelman syndrome. That study, published in the scientific journal PLOS One, demonstrated that mice given GT-AS significantly improved associative learning compared with control Angelman syndrome mice that had not been treated. The findings suggest that such a therapeutic intervention also may  be possible in Angelman syndrome patients. However, more research is needed before the treatment can be used in the clinic.


Last updated: Sept 18, 2019


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