Drug Eluting Embolization Coils for Improved Treatment of Intracranial Aneurysms

用于改善颅内动脉瘤治疗的药物洗脱栓塞弹簧圈

• 批准号: 10020203
• 负责人: Christopher John Bettinger
• 金额: $ 46.18万
• 依托单位: ANCURE, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020203
• 关键词: 3-Dimensional; Aftercare; Anatomy; Aneurysm; Angiography; Animal Model; Berry Aneurysm; Biomimetics; Blood Circulation; Blood Vessels; Brain; Brain Aneurysms; Brain hemorrhage; Catheters; Cerebrovascular system; Clinical; Clinical Research; Coagulation Process; Collagen; Coupled; Crosslinker; Data; Defect; Deposition; Device Designs; Devices; Diffusion; Digestion; Dose; Elastases; Elements; Environmental Wind; Exhibits; Failure; Fiber; Fibrin; Fibrinolysis; Geometry; Histologic; Histology; Human; Implant; In Vitro; Intervention; Intracranial Aneurysm; Kinetics; Measurement; Measures; Mechanics; Microscopy; Modeling; Molds; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Outcome; Performance; Perfusion; Pharmaceutical Preparations; Phase; Plasma; Plasmin; Platinum; Predisposition; Procedures; Process; Proteins; Reaction; Recurrence; Resistance; Risk; Rupture; Safety; Spectrum Analysis; System; Technology; Testing; Therapeutic Embolization; Thrombus; Transport Reaction; Work; base; clinically relevant; crosslink; density; design; drug efficacy; experimental study; genipin; healing; high risk; improved; improved outcome; in vitro Model; in vivo; in vivo evaluation; mechanical properties; minimally invasive; models and simulation; mortality; novel; outcome forecast; pre-clinical; prophylactic; simulation; small molecule; spatiotemporal; thrombogenesis

PROJECT SUMMARY Brain aneurysms are a high-risk condition in which bulging blood vessels in the brain are at risk of rupture. The mortality rate after rupture is 40-60% if no treatment is administered. Current treatment for both ruptured and unruptured aneurysms includes surgical clipping (exovascular therapy) and catheter-based intervention (endovascular therapy). In endovascular therapy, which is the focus of this work, platinum coils are inserted into the aneurysm to induce clotting and exclude the aneurysm from circulation. The primary challenge associated with endovascular aneurysm therapy is the risk of aneurysm recurrence due to mechanical compaction and enzymatic digestion of the clot in the aneurysm sac. Recurrence in intracranial aneurysms elevates the risk of hemorrhagic stroke. This proposal will evaluate the safety and efficacy of a drug-eluting coil to improve outcomes when treating intracranial aneurysms prophylactically. We posit that sustained release of naturally occurring crosslinking agents delivered from drug-eluting endovascular coils will increase the mechanical robustness of the clots, reduce fibrinolysis, and ultimately reduce the risk of recurrence. Clots with increased chemo-mechanical stability will resist failure modes associated with coil compaction and enzymatic degradation. The safety and efficacy of genipin-eluting coils will be evaluated in animal models that are clinically relevant and mimic the anatomy of defects in humans. The safety and efficacy of genipin-eluting coils will be evaluated as a function of dosing and delivery kinetics. In vitro efficacy will be measured using a simulated coiled aneurysm in a model aneurysm sac operating under perfusion. In vivo experiments will be performed using a rabbit elastase aneurysm model. Efficacy will be quantified by angiography, histology, and chemo-mechanical measurements of thrombus in the aneurysms. This project will ultimately measure the in vivo safety and efficacy of drug-eluting coils as a potentially superior technology to treat unruptured anuerysms. Follow-on clinical studies in humans will further establish the safety and efficacy of genipin-eluting embolization coils. Drug-eluting coils have the potential to transform the treatment of unruptured intracranial aneurysms and dramatically reduce the risk of hemorrhagic stroke.

项目概要 脑动脉瘤是一种高风险疾病，大脑中膨出的血管有破裂的风险。这 如果不进行治疗，破裂后的死亡率为 40-60%。目前治疗破裂和 未破裂动脉瘤包括手术夹闭（血管外治疗）和基于导管的干预 （血管内治疗）。在血管内治疗中，这是这项工作的重点，插入铂线圈 进入动脉瘤以诱导凝血并将动脉瘤排除在循环之外。主要挑战 与血管内动脉瘤治疗相关的是机械性动脉瘤复发的风险。 动脉瘤囊中凝块的压实和酶消化。颅内动脉瘤复发 增加出血性中风的风险。该提案将评估药物洗脱线圈的安全性和有效性 改善颅内动脉瘤预防性治疗的结果。我们认为持续释放 从药物洗脱血管内线圈释放的天然交联剂将增加 血栓的机械强度，减少纤维蛋白溶解，并最终降低复发的风险。血栓与 增加的化学机械稳定性将抵抗与线圈压实和酶促相关的故障模式 降解。京尼平洗脱线圈的安全性和有效性将在以下动物模型中进行评估： 具有临床相关性并模仿人体缺陷的解剖结构。京尼平洗脱线圈的安全性和有效性 将根据剂量和递送动力学进行评估。体外功效将使用 在灌注下操作的模型动脉瘤囊中模拟盘绕动脉瘤。体内实验将 使用兔弹性蛋白酶动脉瘤模型进行。疗效将通过血管造影、组织学和 动脉瘤中血栓的化学机械测量。该项目最终将衡量 药物洗脱线圈作为治疗未破裂的潜在优越技术的体内安全性和有效性 动脉瘤。后续人体临床研究将进一步确定京尼平洗脱的安全性和有效性 栓塞线圈。药物洗脱线圈有可能改变未破裂颅内血管瘤的治疗 动脉瘤并显着降低出血性中风的风险。