Preclinical Development of AAV-Galanin for Epilepsy

Period of Performance: 09/30/2008 - 12/31/2009


Phase 1 SBIR

Recipient Firm

Asklepios Biopharmaceutical, Inc.
Chapel Hill, NC 27517
Principal Investigator


DESCRIPTION (provided by applicant): This proposal seeks to leverage proprietary technical advances in Adeno-Associated Virus (AAV) vector mediated gene therapy to develop an AAV based Galanin gene delivery for the treatment of epilepsy. Asklepios Biopharmaceutical, Inc. (Askbio) has obtained intellectual property rights to develop and commercialize an anti-epileptic biologic containing three key technologies: 1.) a gene cassette directing secretion of galanin, 2.) use of a self complementary genome, and 3.) the specifically evolved chimeric AAV2.5 capsid. The incorporation of these technologies into a viable alternative gene therapy for epilepsy is a novel component of this proposal, and on that offers a great deal of hope to the estimated 350-700K patients in the U.S. for whom anti-epileptic drugs fail. The feasibility experiments detailed in this Phase I proposal will determine an efficacious dose range for the chimeric AAV2.5 containing a self-complementary FIB-Galanin transgene cassette (dsAAV2.5 FIB-GAL), as well as examine the efficacy and safety of intracranial administration of dsAAV2.5 FIB-GAL to treat Mesiotemporal lobe epilepsy (MTLE) using two different mouse models of limbic seizure, focal electrical kindling and peripheral kainic acid administration. We fully expect the results of the proposed studies to support advancing to a Phase II study consisting of definitive preclinical studies, in both rodent and large animal models, as well as pivotal safety and toxicology studies in support of an IND submission. The proposed initial clinical study will be undertaken in subjects with MTLE, who are already candidates for surgical resection, and will employ a study design involving gene delivery prior to scheduled resection of epileptogenic/dsAAV2.5 FIB-GAL infused tissue. PUBLIC HEALTH RELEVANCE: Asklepios Biopharmaceutical, Inc. is developing a therapeutic to treat people with Mesiotemporal lobe epilepsy (MTLE). Current treatment strategies are limited to anti-epileptogenic drugs, most of which are several decades old. For the 350-700K patients in whom drug therapies fail to resolve seizures, surgical resection offers a potential resolution. The proposed therapeutic, an AAV-mediated delivery of Galanin, is designed to provide an alternative therapy to meet this longstanding medical need.