Biomimetic Membrane Device for Therapeutic Application in Chronic Heart Failure

仿生膜装置在慢性心力衰竭治疗中的应用

基本信息

批准号：
8831237
负责人：
DEBORAH Ann BUFFINGTON
金额：
$ 65.52万
依托单位：
INNOVATIVE BIOTHERAPIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8831237
关键词：
Accounting Acute Animal Disease Models Animal Model Arrhythmia Binding Biological Response Modifier Therapy Biomimetics Biotechnology Blood Brain natriuretic peptide Calcium Canis familiaris Cardiopulmonary Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cessation of life Chronic Citrates Clinical Clinical Treatment Clinical Trials Congestive Heart Failure Critical Illness Data Development Devices Disease Dose End stage renal failure Exposure to FDA approved Fiber Functional disorder General Population Goals Grant Heart Transplantation Hospitalization Hour Immune System Diseases Immune system Inflammation Inflammatory Insulin Resistance Kidney Kinetics Left Length Leukocytes Levosimendan Marketing Mediation Medical Membrane Metabolic syndrome Modeling Myocardial Neurosecretory Systems Non-Insulin-Dependent Diabetes Mellitus Organ Outcome Patients Performance Phase Phase III Clinical Trials Procedures Process Recombinants Regenerative Medicine Relative (related person)Risk Sepsis Septic Shock Staging Survival Rate Symptoms System Target Populations Technology Testing Therapeutic Therapeutic Effect Translations Ventricular Work acute stroke base clinical application clinical efficacy commercialization cost design effective therapy immunoregulation improved innovation macrophage meetings monocyte mortality novel outcome forecast polysulphone pre-clinical programs public health relevance research study ventricular assist device

项目摘要

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.

描述（由适用提供）：心血管疾病是美国死亡率的主要原因，占所有死亡的45％。慢性心力衰竭（CHF）现在被理解为一种多系统疾病过程，不仅涉及心血管系统，还涉及肾脏，神经内分泌和免疫学系统。目前尚无有效的疗法来治疗最严重的CHF患者急性代偿HF的患者。一种非常规的方法来减少与CHF慢性炎症状态相关的心脏抑制作用，可能为这种疾病提供突破性的疗法。该建议将评估犬CHF模型中免疫调节装置的有效性，以确定转化为临床应用和事件商业化的机会。这产品：仿生膜装置（BMD）是一种免疫调节的，旨在调节与CHF相关的心脏抑制作用的靶向体外纤维膜装置。 BMD是一种侧重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的平台技术。 BMD多硫酮纤维通过体外电路选择性地隔离了激活的全身性白细胞。在初步研究中，BMDCHF在CHF的犬类模型中显示出有希望的治疗益处。内向：关于当前的HF疗法策略，BMDCHF是一种完全不同的创新方法来治疗CHF。 BMDCHF并没有利用小型药物分子来改善心肌收缩力，而是作为一种免疫调节装置来抑制CHF慢性炎症状态的心脏抑制作用。长期目标：该提案将为BMDCHF对CHF的影响提供概念证明，以期在治疗后长达4周。第一阶段的假设：计划的实验将证明在CHF的犬类模型中经过6个小时BMDCHF治疗课程后，心血管表现的改善。 AIM 1：评估治疗后48小时的CHF犬模型中3 x 6小时BMDCHF会话的影响。 AIM 2：在治疗后1和4周评估CHF犬模型中的BMDCHF治疗。 II期目标：II期计划将评估BMDCHF最佳剂量（相对于会话的数量和长度）和长期影响（3-6个月）对CHF犬模型中对心血管和炎症参数的治疗作用对心血管和炎症参数的影响。商业机会：在I和II期研究计划过程中产生的数据将纳入IDE提交给FDA的临床前部分，以测试BMDCHF治疗CHF。仅在美国，这些迹象的市场每年都超过$ 30B。