Coronary artery disease affects 12 million Americans and is the number on killer in the United States. Diabetes affects over 16 million Americans, with more than 80,000 new cases diagnosed each year. Cardiovascular complications of diabetes kills 75% of diabetics. Routine clinical management for coronary artery disease involves percutanesous transluminal coronary angioplasty (PTCA) and coronary artery stenting (CAS). Re-narrowing of an opened coronary artery (restenosis) occurs in approximately 50% of patients within six months of PTCA and in 35% of patients following CAS and requires intervention. Currently, a bottleneck exists in pre-clinical testing arena for new technology and therapeutics due to limits of current animal models that threatens to handicap R&D efforts. Hence, the major long-term objective of this proposal is to develop and validate a novel in-stent stenosis animal model system to accelerate advances in CAD therapeutics and device testing. This patented technology will combine advances in stent design and scale with a well-characterized model of Type2 diabetes and offer via licensing agreement, a potential powerful system to also study vascular restenosis. Biomedical Research Models, Inc. requests SBIR Phase I funding to test the feasibility of a new stent design rat model system to study in-stent stenosis.
Specific Aim 1 will involve the manufacture of BRM ministents and deliver devises (balloon catheter) according to specifications. The mini-stent will then be fatigue-tested according to industry standards. Also, Specific Aim 1 will compare the BRM mini-stent and balloon catheter relative to commercial stent in normal BBZDR lean rats for a period of 8 weeks. Stents will be deployed in the left common carotid artery of two cohorts of twelve rats each. Animal health will be monitored and gross pathology will be recorded at necropsy. In-stent and uninjured segments of carotid arteries will be fixed, resin-embedded and sectioned for histopathology, post mortem. Differences in stent integrity, vessel injury, and in stent stenosis will be reported. Success will be judged relative to pathology and stenosis reported.
In Specific Aim 2, the BRM mini-stent will be tested in the BBZDR/Wor rat, a well -characterized model of Type 2 diabetes. A cohort of 12 obese diabetic (4 months duration) will be compared to an age-matched cohort of lean non-diabetic BBZDR/Wor rats. Similar endpoint analyses will be performed as described in Specific Aim 2. In Phase II, data collected using this animal model system will be used to identify novel biomarkers of stenosis and further explore this model system as drug delivery platform to screen potential novel therapies for CAD.
