Muscle Specific Gene Therapy for Ischemia

Period of Performance: 09/24/1998 - 08/31/1999


Phase 2 SBIR

Recipient Firm

Valentis, Inc.
Burlingame, CA 94010
Principal Investigator


The new technology developed during Phase I offers a novel approach to treating ischemia effectively and safely. We developed muscle-specific promoters that provide higher levels of expression than natural promoters and altered regulatory properties. The aim of the Phase II research is to apply these advances to develop non-viral gene medicines that will stimulate angiogenesis and provide a safe and effective therapy for ischemia. GENEMEDICINE has developed a novel approach using polymeric formulations to enhance gene delivery. We have shown in rats that IM injection of muscle-specific GH gene medicine formulated in PVP resulted in levels 10-15-fold higher than the plasmid in saline. This proposal describes the development of a muscle-specific plasmid that expresses hVEGF. The hVEGF expression plasmid will be optimized for high level, tissue-restricted expression by including a synthetic muscle-specific promoter and a hVEGF coding sequence that contains optimized human codons. The muscle-specific gene medicine will consist of the muscle- specific, codon optimized hVEGF expression plasmid complexed with the polymeric gene delivery system. As such, it has significant advantages over the CMV-based plasmids delivered in saline developed by others. The gene medicine will be tested in the rabbit ischemia model and the preclinical studies completed for clinical trials. PROPOSED COMMERCIAL APPLICATIONS: Currently, the prognosis for patients with chronic critical leg ischemia is grim. Approximately 150,000 people per, year have been reported to have ischemia severe enough to require lower limb amputation because they are unresponsive to conventional medical or surgical treatment. Following amputation, the mortality rate is high. There is a compelling need for effective treatment strategies.