Novel Anti-Inflammatory To Treat Atherosclerosis

描述（由申请人提供）：心血管和脑血管疾病，包括冠状动脉疾病（CAD）、外周动脉疾病（PAD）、心脏病发作、缺血性卒中和短暂性脑缺血发作（TIA），是西方世界的头号死亡原因，并且具有共同的潜在致病机制动脉粥样硬化。动脉粥样硬化是一种缓慢进行性的硬化和狭窄的动脉所造成的斑块的积累，最终限制血流到重要器官。当斑块变得不稳定并脱离动脉壁时，它会导致血液凝块部分或完全阻塞血流，导致缺氧和潜在的死亡。受动脉粥样硬化影响的人群的规模以及与疾病的各种表现相关的社会经济成本需要开发有效的治疗方法。 人们已经达成共识，炎症在动脉粥样硬化的发展和进展中起决定性作用，因此，代表了一个新的潜在治疗靶点。为此，我们开发了一种载脂蛋白E（apoE）模拟抗炎肽，COG133，其显著抑制巨噬细胞和/或小胶质细胞释放炎性细胞因子和炎性自由基。 这些报告表明，COG133在许多体外和体内范例中表现出抗炎活性，因此，具有动脉粥样硬化治疗所必需的许多性质。 具体目的1：使用动脉粥样硬化的apoE-KO小鼠模型来检验COG133将调节以下的假设： A）血清中的细胞因子水平：IL-2、IL-4、IL-5、IL-10、IL-12、GM-CSF、IFN-γ、TNF-α、IL-6和IL-8 B）血清中的脂蛋白水平：用COG 133处理的apoE-KO小鼠的总血浆胆固醇和甘油三酯以及血浆VLDL、LDL、HDL及其各自的血清亚类的量 C）胸腹主动脉斑块体积 这些I期研究的结果将允许初步评估采用COG133作为新型抗动脉粥样硬化剂的可行性，所述抗动脉粥样硬化剂可以抑制和/或预防动脉粥样硬化潜在的免疫功能障碍。Cognosci Inc.的总体目标是开发一种治疗动脉粥样硬化的新方法。

DESCRIPTION (provided by applicant): Cardiovascular and cerebrovascular diseases including coronary artery disease (CAD), peripheral artery disease (PAD), heart attack, ischemic stroke, and transient ischemic attack (TIA), are the number one cause of mortality in the Western world and have a common underlying pathogenic mechanism, atherosclerosis. Atherosclerosis is a slow progressive hardening and narrowing of the arteries caused by buildup of plaque which ultimately restricts blood flow to vital organs. When a plaque becomes unstable and breaks away from the artery wall, it can cause a blood clot that partially or totally blocks blood flow, resulting in oxygen starvation and potentially death. The magnitude of the population affected by atherosclerosis and the socioeconomic costs associated with various manifestations of the disease necessitates the development of an effective treatment. A consensus has emerged that inflammation plays a decisive role in the development and progression of atherosclerosis, and, as such, represents a new potential therapeutic target. To this end, we have developed an apolipoprotein E (apoE) mimetic anti-inflammatory peptide, COG133, which significantly inhibits release of inflammatory cytokines and inflammatory free radicals from macrophages and/or microglia. These reports indicate that COG133 exhibits anti-inflammatory activity in a number of in vitro and in vivo paradigms, and therefore, possesses many of the properties necessary for a therapy for atherosclerosis. Specific Aim 1: Use the apoE-KO mouse model of atherosclerosis to test the hypothesis that COG133 will modulate the following: A) cytokine levels in serum: IL-2, IL-4, IL-5, IL-10, IL-12, GM-CSF, IFN-gamma, TNF-alpha, IL-6 and IL-8 B) lipoprotein levels in serum: total plasma cholesterol and triglycerides as well as amounts of plasma VLDL, LDL, HDL and their respective subclasses in serum of apoE-KO mice treated with COG133 C) volume of plaque in thoraco-abdominal aorta The outcome of these Phase 1 studies will permit a preliminary evaluation of the feasibility of employing COG133 as a novel anti-atherogenic agent that can inhibit and/or prevent the immune dysfunction underlying atherosclerosis. The overall goal of Cognosci Inc. is to develop a novel therapy for atherosclerosis.