Biomimetic Membrane Device for Therapeutic Application in Chronic Heart Failure

 描述（由申请方提供）：心血管疾病是美国的主要死亡原因，占所有死亡的45%。慢性心力衰竭（CHF）是一种多系统疾病，不仅涉及心血管系统，还涉及肾脏、神经内分泌和免疫系统。目前没有有效的治疗方法可用于治疗最严重的急性失代偿性HF CHF患者亚组。一种非传统的方法来减少与慢性炎症状态的CHF相关的心脏功能的影响，可能会提供一个突破性的治疗这种疾病。本提案将评价免疫调节器械在犬CHF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。的 产品名称：仿生膜装置（BMD）是一种免疫调节性体外纤维膜装置，旨在调节与CHF相关的心脏功能效应。BMD是一种平台技术，专注于与急性和慢性器官功能障碍相关的急性和慢性炎症的免疫调节。BMD聚砜纤维选择性地隔离激活的全身白细胞，因为它们通过体外回路流过纤维套管。在初步研究中，BMDCHF在CHF犬模型中显示出有希望的治疗益处。注意：就目前的HF治疗策略而言，BMDCHF是治疗CHF的一种完全不同的创新方法。BMDCHF不是利用小的药理学分子来改善心肌收缩性，而是作为免疫调节装置来抑制CHF的慢性促炎状态的心脏收缩作用。长期目标：本提案将为BMDCHF对CHF治疗后长达4周的影响提供概念验证。第一阶段假设：计划的实验将证明在CHF犬模型中进行多次6小时BMDCHF治疗后心血管性能的改善。目的1：在治疗后48小时评估3 x 6小时BMDCHF治疗对CHF犬模型的影响。目的2：在治疗后1周和4周评估CHF犬模型中的BMDCHF治疗。第二阶段目标：II期计划将在CHF犬模型中评估BMDCHF最佳剂量（关于疗程次数和持续时间）和对心血管和炎症参数的长期影响（3 - 6个月）。商业机会：I期和II期研究计划过程中生成的数据将纳入向FDA提交的IDE申请的临床前部分，以检测BMDCHF治疗CHF的效果。仅在美国，这些适应症的市场每年就超过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.