Pilot Feasibility of an Enzyme Replacement Therapy for AS

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FAST and FAST Canada are pleased to announce a grant to UC Davis.  David Segal, Ph.D. and his UC Davis lab have received funding to determine if enzyme replacement therapy (ERT) alleviates the symptoms of Angelman syndrome (AS) in animal models.  Individuals with Angelman syndrome lack a working copy of the UBE3A gene.  The UBE3A gene, provides instructions for making a protein called ubiquitin protein ligase E3A.  Ubiquitin protein ligases are enzymes that target other proteins for degradation or upregulation and because the UBE3A gene is either missing or mutated in individuals with Angelman syndrome, what happens is the UBE3A protein is not produced in order to perform this very important function.  An AS-ERT would provide the missing UBE3A enzyme as a purified protein. It will be modified to enter neurons and function both intra- and extra-cellularly, which new data supports is very important.

ERTs have been used for over 10 years in treatments for various enzyme deficiency syndromes.  ERTs are a potentially promising therapeutic as they are non-permanent and have a good safety profile.

Dr. Segal’s team will develop an AS-ERT and demonstrate its efficacy using in-vitro cell models, as well as evaluate the efficacy of AS-ERT in the mouse model. This study would be a first step – a proof of concept – in developing an ERT to potentially treat AS.

Dr. David Segal is a UC Davis professor of Biochemistry and Molecular Medicine with joint appointments in the Genome Center, the MIND Institute, and the Department of Pharmacology.  His area of expertise is in gene editing.