RIBOZYMES FOR THE PREVENTION OF RESTENOSIS AFTER PTCA

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Chimeric ribozyme-based therapeutics targeting Proliferating Cell Nuclear Antigen (PCNA) have been identified and shown to prevent vascular smooth muscle cell proliferation that is a major contributing factor in restenosis. Preclinical studies in rat and porcine stenosis models show dramatic, statistically significant, angiographic and histomorphological evidence of reduction in the experimental stenosis rate in treated versus control arteries. Successful inhibition of vascular smooth muscle cell proliferation following percutaneous transluminaI coronary angioplasty (PTCA) and stent placement would constitute a major advance in the treatment of coronary artery' disease. At the completion of the phase I portion of this application Immusol has optimized both the chimeric ribozyme structure, and the stability of its prototype PCNA targeted ribozyme, and has shown effective inhibition of stenosis in the porcine stent model by direct delivery of the drug via an available, FDA-approved infusion device prior to PTCA. This portion of the study will establish the reproducibility of the drug manufacturing process, examine the dose effect of this drug, and establish its safety in porcine and rat models in preparation for a clinical trial of safety and efficacy in patients. PROPOSED COMMERCIAL APPLICATIONS: Immusol, Inc. plans to develop PCNA targeted ribozymes for use in the prevention of restenosis following PTCA.