Biomimetic Membrane Device for Therapeutic Application in Chronic Heart Failure

 描述(申请人提供)：心血管疾病是美国死亡的主要原因，占所有死亡人数的45%。慢性心力衰竭(CHF)现在被认为是一个多系统的疾病过程，不仅涉及心血管系统，而且还涉及肾脏、神经内分泌和免疫系统。目前还没有有效的治疗方法来治疗最严重的慢性心力衰竭急性失代偿性心衰患者。一种非传统的方法来减少与慢性炎症状态CHF相关的心脏抑制效应，可能为这种疾病提供突破性的治疗方法。这项建议将评估免疫调节装置在犬心力衰竭模型中的有效性，以确定转化为临床应用和最终商业化的机会。这个 产品：仿生膜装置(BMD)是一种免疫调节体外纤维膜装置，旨在调节与充血性心力衰竭相关的心脏抑制效应。BMD是一种平台技术，专注于免疫调节与急性和慢性器官功能障碍相关的急性和慢性炎症。当激活的全身性白细胞通过体外循环流经纤维外壳时，骨密度聚砜纤维选择性地隔离激活的白细胞。在初步研究中，BMDCHF在犬CHF模型中显示出良好的治疗效果。创新：就目前的心力衰竭治疗策略而言，BMDCHF是一种完全不同的、创新的治疗CHF的方法。BMDCHF不是利用小的药物分子来改善心肌收缩能力，而是作为一种免疫调节装置来抑制CHF慢性促炎状态的心脏抑制效应。长期目标：该提案将为BMDCHF在治疗后4周内对CHF的影响提供概念验证。第一阶段假设：计划中的实验将证明，在CHF犬模型中，经过多次6小时的BMDCHF治疗后，心血管功能得到改善。目的1：评估3x6小时BMDCHF治疗对犬CHF模型治疗后48小时的影响。目的：在心力衰竭犬模型中评价治疗1周和4周后BMDCHF的治疗效果。第二阶段目标：第二阶段计划将评估BMDCHF的最佳剂量(关于疗程的次数和时间)以及对CHF犬模型的心血管和炎症参数的长期影响(3-6个月)。商业机会：在第一阶段和第二阶段研究计划过程中产生的数据将被纳入向FDA提交的IDE提交的临床前部分，用于测试BMDCHF在治疗CHF方面的作用。仅在美国，这些指征的市场规模每年就超过300亿美元。

 DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of mortality in the US, accounting for 45% of all deaths. Chronic Heart Failure (CHF) is now understood to be a multi-system disease process which involves not only the cardiovascular system but also the renal, neuroendocrine and immune systems. There is no effective therapy currently available to treat the most severe subset of CHF patients with acute decompensated HF. An unconventional approach to reduce the cardiodepressant effects associated with the chronic inflammatory state of CHF may provide a breakthrough therapy for this disorder. This proposal will evaluate the efficacy of an immunomodulatory device in a canine CHF model to identify opportunities for translation to clinical applications and eventual commercialization. The Product: The Biomimetic Membrane Device (BMD) is an immunoregulating, extracorporeal fiber membrane device targeted to modulate the cardiodepressant effects that are associated with CHF. BMD is a platform technology focused on immunomodulation of the acute and chronic inflammation associated with acute and chronic organ dysfunction. BMD polysulfone fibers selectively sequester activated systemic leukocytes as they flow through the fiber casing via an extracorporeal circuit. In preliminary studies, the BMDCHF has shown promising therapeutic benefit in a canine model of CHF. In- novation: In regard to current HF therapeutic strategies, the BMDCHF is a totally different, innovative approach to treat CHF. Rather than utilizing small pharmacologic molecules to improve myocardial contractility, the BMDCHF acts as an immunomodulatory device to dampen the cardio-depressant effects of the chronic pro- inflammatory state of CHF. Long Term Goal: This proposal will provide proof-of-concept for impact of the BMDCHF on CHF for up to 4 weeks post therapy. Phase I Hypothesis: The planned experiments will demonstrate improvement of cardiovascular performance after multiple 6 hour BMDCHF therapy sessions in a canine model of CHF. Aim 1: Assess impact of 3 x 6 hour BMDCHF sessions in a canine model of CHF at 48 hours post therapy. Aim 2: Assess BMDCHF therapy in a canine model of CHF at 1 and 4 weeks post therapy. Phase II Objective: The Phase II plan will assess BMDCHF optimal dose (with respect to number and length of sessions) and long term impact (3 -6 months) of therapeutic effect on cardiovascular and inflammatory parameters in a canine model of CHF. Commercial Opportunity: The data generated during the course of the Phase I and II study plans will be incorporated into the pre-clinical section of an IDE submission to the FDA for testing of the BMDCHF in the treatment of CHF. The market for these indications exceeds $30b annually in the US alone.