Novel Guidewire Design and Coating for Adenosine Delivery

冠状动脉疾病（CAD）影响了1400万美国人，导致大约90万心肌

Coronary artery disease (CAD) effects 14 million Americans resulting in approximately 900,000 myocardial infarction’s (MI) and 650,000 deaths annually. Percutaneous intervention (PCI) is the most frequently performed procedure to treat CAD. Microvascular obstruction (MVO) and “no reflow phenomenon” (NRF) are major barriers that preclude optimal outcomes and are independent risk factors for mortality and heart failure. Current devices are only partially effective in mitigating MVO and NRF following PCI for MI. The mechanisms responsible for MVO are complex and multifactorial. Adenosine, an endogenous nucleoside, attenuates many of the mechanisms responsible for MVO. Seminal studies in our laboratory demonstrated that intravenous adenosine resulted in striking myocardial protection, a finding confirmed in large clinical trials. Adenosine’s full therapeutic potential is compromised due to its ultrashort half-life (approximately 1 second) in human blood. By combining guidewire design, surface chemistry, jet milling of adenosine and creation of novel hydrophilic drug-loading and diffusion barrier coatings, we developed a guidewire platform (Adenowire) which allows for continuous delivery of adenosine throughout a PCI procedure. In vitro studies confirmed an ideal elution profile for adenosine that was verified in large animal models where robust vasodilatation and rapid reversal of vasoconstriction was identified. The novel inert coating also provides antiplatelet effects that are amplified with the addition of adenosine in the coating. Bench studies reveal that wire performance and coating quality are comparable to inert hydrophilic commercially available guidewires. While our phase 2 SBIR grant and subsequent development resulted in a safe and functional product, a significant funding gap remains before the device can be commercialized. Manufacturing and coating of Adenowires were not subjected to rigorous FDA regulatory requirements and utilized a non-sterilized product. Adenowire is classified as a combination product and both adenosine and guidewires are already FDA approved. A pre-IND submission by a regulatory consultant determined that approval would occur via CDRH (device) division utilizing a “de novo“ pathway. In order to proceed with clinical trials, the following assistance is needed: 1) Late Stage Research and Development on guidewire manufacturing and application of coating utilizing good manufacturing practice (GMP) and evaluation of biocompatibility and functional parameters on a sterilized product; 2) Regulatory Assistance to include strategy, documentation, submission of IDE application and determination of size of requirements for clinical trials. Results obtained from these studies would be invaluable since such data would result in finalization of the product allowing issuance of an IDE and initiation of a First in Man (FIM) clinical trial. This will greatly enhance our ability to obtain additional funding and strategic partnerships. Adenowire is a transformative device that is inexpensive, will have a large target market and represents a major technological advancement for treating CAD patients with PCI.