CAMBRIDGE, Mass.–(BUSINESS WIRE)–Agilis Biotherapeutics, Inc. (Agilis), a biotechnology company advancing innovative DNA therapeutics for rare genetic diseases that affect the central nervous system (CNS), announced today two presentations on its gene therapy program for Angelman syndrome (AS). A poster presentation entitled, “The A-BOM: Collaborating to identify patient-centered biomarkers and outcome measures for Angelman Syndrome” was presented on October 16, 2017, at the National Organization for Rare Diseases (NORD) Rare Disease Summit in Washington, D. C., by Terry Jo Bichell, Ph.D., Scientific Officer of Angelman Syndrome Biomarker and Outcome Measures (A-BOM) Alliance for which Agilis is a founding member. Additionally, an abstract entitled, “Expression of Human UBE3A via AAV5 Rescues Spatial Learning and Synaptic Plasticity Deficits in a Model of Angelman Syndrome” was presented on October 19, 2017, at the annual meeting of the European Society of Gene and Cell Therapy (ESGCT), by Kevin Nash, Ph.D., Agilis’ collaborator at the University of South Florida (USF). AS is a rare neurological disorder caused by a loss of function of the maternal UBE3A gene in the brain, resulting in global developmental delay, severe cognitive disruption, deficits in learning and memory, lack of speech, seizures, tremors, and ataxic gait. According to The Foundation for Angelman Syndrome Therapeutics, AS has an estimated newborn incidence of 1 in 15,000 live births.
Kevin Nash, Ph.D., from USF, presented recent in vivo data from Agilis’ gene therapy approach to treat AS at the 2017 ESGCT Annual Meeting, an important venue for the gene and cell therapy community driving innovation in these fields and a preeminent conference in Europe bringing together top gene and cell therapy professionals and featuring groundbreaking scientific and clinical trial results and cutting-edge technological advancements. Using the gold-standard murine knock-out model for AS (AS mice), an adeno-associated virus (AAV) vector with the human UBE3A gene delivered to the central nervous system (CNS) was evaluated. Encouraging evidence showing rescue of phenotypes associated with AS was observed. Intracerebroventricular (ICV) delivery of rAAV expressing human UBE3A in adult AS mice resulted in widespread biodistribution throughout the CNS and significant functional expression of hUBE3A. Ex vivo assessments of hippocampal electrophysiology revealed restoration of long-term potentiation (LTP), a key measure of neuronal activity believed to be important in memory and learning. Restoration of LTP, in turn, was correlated with recovery of functional capabilities affected in the AS mouse model and characteristic of AS patients, including spatial learning in the hidden platform water maze test. AAV-dependent hUBE3A expression recovers the severe defect in hippocampal synaptic plasticity and is sufficient to rescue learning and memory phenotypes in adult AS mice. These data extend earlier studies published by Dr. Nash and colleagues and demonstrate for the first time that ICV delivery of the human UBE3A gene can recover the major AS mouse model phenotypes in support of further development of the Company’s CNS-targeted AAV approach toward human clinical trials.
“The presentation of our new data on Angelman syndrome gene therapy at ESGCT continues to validate Agilis’ approach to development of our gene therapy program for Angelman syndrome,” said Jodi Cook, Ph.D., Chief Operating Officer for Agilis.
Terry Jo Bichell, Ph.D., Scientific Officer of A-BOM Alliance said, “We were delighted to share our experience with other rare disease groups at the NORD conference. We have a great model of pre-competitive cooperation that was initiated by Agilis Biotherapeutics, and because of this, progress has accelerated to finding treatments for Angelman syndrome. The NORD Rare Diseases Summit brings together all stakeholders in rare diseases including government officials, researchers, clinicians, patients, families, advocates, and industry.”
The A-BOM alliance focuses on advancing the understanding of AS and identifying and evaluating specific biomarkers and outcome measures that will be necessary for evaluating therapeutics in clinical trials through five focus areas: Quality of life (including sleep); Cognition (including language); Development (including motor skills and the use of validated scales); Biological tissues (including plasma and CSF measures); and Seizures (EEG measurements). The goal of the effort is to develop pilot data to define areas for further development with more comprehensive study. The Alliance operates to share data from all the projects with all of the members at meetings held twice a year.
Jodi Cook, Ph.D., Chief Operating Officer of Agilis, said, “As a pioneer industry partner with the Angelman community, we are thrilled to see the important and material advances being made in fundamental areas in the understanding of AS that are a result of the A-BOM alliance. We look forward to the enablement these efforts will bring to the development and evaluation of novel therapeutics for those living with AS.”
About Angelman syndrome
Angelman syndrome (AS) is a rare disorder caused by the loss of function of the maternal UBE3A gene encoding the ubiquitin ligase E6-AP, a protein which plays a critical role in the function of the central nervous system. AS presents with symptoms of delayed motor development, severe learning disability, absent speech, seizures, and ataxia, resulting in chronic disability and the need for lifelong care. According to The Foundation for Angelman Syndrome Therapeutics, the disorder strikes an estimated 1 in 15,000 live births.
About Agilis Biotherapeutics, Inc.
Agilis is a clinical stage company advancing innovative gene therapies designed to provide long-term efficacy for patients with debilitating, often fatal, rare genetic diseases that affect the central nervous system. Agilis’ gene therapies are engineered to impart sustainable clinical benefits by inducing persistent expression of a therapeutic gene through precise targeting and restoration of lost gene function to achieve long-term efficacy. Agilis’ rare disease programs are focused on gene therapy for AADC deficiency, Friedreich ataxia, and Angelman syndrome, all rare genetic diseases that include neurological deficits and result in physically debilitating conditions.
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