Cardiovascular disease secondary to atherosclerosis is the leading cause of death in the United States. Current percutaneous vascular interventions that treat severe atherosclerosis require inflation of a balloon with or without deployment of a rigid, non-compliant metal stent. Yet, this technique fails to remove the atherosclerotic plaque burden and causes mechanical trauma to the arterial wall, resulting in significant restenosis rates. FDA-approved plaque debulking technologies do exist and are used in the clinical arena. However, to debulk the plaque, each of these therapies induces some form of mechanical or thermal injury to the vessel wall, which ultimately stimulates the development of neointimal hyperplasia and results in significant arterial restenosis. Therefore, the goal of this study is to develop a novel endovascular technology to reduce atherosclerotic plaque burden without inducing thermal or mechanical trauma to the arterial wall. Our paradigm-shifting technology is based on a safe method of digesting atherosclerotic plaque in situ through the use of a double occlusion balloon catheter, sonication wire, and a highly customized solution tailored to safely digest atherosclerotic plaque. Given that most atherosclerotic plaques are composed of collagen, fibrin, lipids, proteoglycans, inflammatory cells, smooth muscle cells, and calcium, we hypothesize that a digestion solution containing agents that target these plaque components will dissolve and digest the plaque in situ within a clinically relevant time frame. Avoidance of the use of elastases in our solution limits digestion of the plaque to the elastic lamina. With our multidisciplinary team of investigators, we have already demonstrated the feasibility and initial safety of our approach through preliminary data. We have demonstrated effective digestion of excised human carotid artery atherosclerotic plaques as well as the plaque inside intact human superficial femoral arteries. We have evaluated our approach in a non-atherosclerotic porcine model in vivo and showed that our therapy did not injure the arterial wall, was limited to the internal elastic lamina, and did not result in dissections or aneurysm formation, suggesting that our therapy is safe. Lastly, we evaluated our approach in an atherosclerotic porcine model and demonstrated initial efficacy at reducing plaque without inducing thrombosis or aneurysmal degeneration. Given the feasibility and promise of these preliminary data, we believe further scientific exploration and development of this novel technology is warranted and will lead to an innovative clinical therapy for the treatment of atherosclerosis in humans. Thus, the overall objective of this proposal is to robustly evaluate the safety, efficacy, durability, and repeatability of this therapy in a preclinical porcine animal model of atherosclerosis. Successful completion of these studies will directly lead to an FDA application for a first-in-human Phase 1 clinical trial, and is thus highly aligned with the mission of the National Institutes of Health to ?enhance health, lengthen life, and reduce illness and disability? through the application of new knowledge.

Public Health Relevance

Cardiovascular disease secondary to atherosclerosis is the leading cause of death in the United States. Current percutaneous endovascular interventions aimed at treating severe atherosclerosis include balloon angioplasty with or without stenting, or plaque debulking. While each of these therapies enlarge the inside of the artery, each unfortunately causes thermal or mechanical trauma to the artery wall, which results in significant restenosis rates. This proposal seeks to develop and optimize an innovative, paradigm-shifting technology to treat atherosclerosis by removing atherosclerotic plaques inside the artery atraumatically using a specialty catheter, sonication wire, and a highly-tailored solution targeted to digest the individual components of atherosclerotic plaque.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Lee, Albert
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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