Therapeutic to Reduce Acute Inflammation Following Cardiac Ischemia

减少心脏缺血后急性炎症的治疗

• 批准号: 7109773
• 负责人: ELISABETH M ALICOT-CARROLL
• 金额: $ 12.92万
• 依托单位: DECIMMUNE THERAPEUTICS, INC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109773
• 关键词: affinity chromatography; antiantibody; antigen antibody reaction; biological models; cardiovascular disorder therapy; enzyme linked immunosorbent assay; gene expression; genetically modified animals; immunoglobulin M; immunotherapy; inflammation; laboratory mouse; myocardial ischemia /hypoxia; myosins; pathologic process; protein binding; protein structure; reperfusion; surface plasmon resonance

DESCRIPTION (provided by applicant): Reperfusion injury (Rl) is a serious life-threatening inflammatory process of unknown etiology that occurs when blood flow is returned to an ischemic tissue, for example heart muscle following a heart attack or cardiac surgery. The restoration of blood flow to previously ischemic tissue results in cardiac inflammation and tissue damage. Studies at Declmmune have now proven the pivotal role natural antibodies play in the initiation of Rl. The company has isolated the first pathogenic natural antibody in a mouse model, identified the specific ischemic antigen target of this antibody, and prepared peptide mimetopes. These peptides, when administered prior to or shortly after ischemia, block reperfusion injury to intestine and hind limb muscle in mice and prevent myocardial infarction following ischemia and reperfusion in the mouse heart. The aim of this grant is to determine if the specificity of the natural antibody and ischemic antigen identified in mice is conserved in humans. The research design will utilize the reagents and animal models that have been developed in the mouse studies and apply them to the evaluation of human tissue and blood samples. A successful outcome will lead to the development of a therapeutic compound to be used to prevent acute inflammation following cardiac ischemia. The company anticipates that its first product will be either a peptide or a blocking agent (e.g., antibody, aptimer, or other binder) that will be administered to patients prior to open heart surgery. More than 690,000 open heart procedures are performed in the US annually. Approximately 12% of these patients die or have a heart attack within 6 months of surgery and Rl is a major cause. In addition the compound could have significant potential in treating patients following myocardial infarction or stroke.

描述（由申请人提供）：再灌注损伤（RL）是一种严重威胁生命的未知病因炎症过程，当血流恢复到缺血性组织时，例如心脏病或心脏病手术后心肌。血液流向先前缺血性组织的恢复会导致心脏炎症和组织损伤。 现在，在Declmmune进行的研究已经证明了自然抗体在RL启动中起关键作用的作用。该公司在小鼠模型中分离了第一种致病天然抗体，鉴定了该抗体的特定缺血抗原靶标，并制备了肽Mimetopes。这些肽是在缺血之前或不久后服用的，会阻塞小鼠的肠道和后肢肌肉的再灌注损伤，并防止小鼠心脏缺血和再灌注后心肌梗塞。 这项赠款的目的是确定在小鼠中鉴定出的天然抗体和缺血性抗原的特异性是否在人类中是保守的。研究设计将利用小鼠研究中开发的试剂和动物模型，并将其应用于人体组织和血液样本的评估。 成功的结果将导致一种治疗化合物的发展，以防止心脏缺血后预防急性炎症。该公司预计其第一种产品将是肽或阻塞剂（例如抗体，适应性或其他粘合剂），该产品将在开放心脏手术前向患者施用。每年在美国进行超过690,000次开放心脏手术。这些患者中约有12％在手术后6个月内死亡或心脏病发作是主要原因。此外，该化合物在心肌梗塞或中风后治疗患者可能具有巨大的潜力。