Novel Anti-Inflammatory To Treat Atherosclerosis

描述(申请人提供)：心脑血管疾病，包括冠状动脉疾病(CAD)、外周动脉疾病(PAD)、心脏病发作、缺血性中风和短暂性脑缺血发作(TIA)，是西方世界的头号死亡原因，具有共同的潜在致病机制，即动脉粥样硬化。动脉粥样硬化是由斑块积聚引起的动脉缓慢进行性硬化和狭窄，最终限制流向重要器官的血液。当斑块变得不稳定并脱离动脉壁时，它可能会引起血栓，部分或全部阻止血液流动，导致缺氧，甚至可能死亡。受动脉粥样硬化影响的人口规模之大，以及与疾病的各种表现相关的社会经济代价，都要求开发有效的治疗方法。 目前已达成共识，认为炎症在动脉粥样硬化的发生和发展中起着决定性的作用，因此，它代表了一个新的潜在的治疗靶点。为此，我们开发了一种载脂蛋白E(ApoE)模拟抗炎肽COG133，它能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显示出抗炎活性，因此具有许多治疗动脉粥样硬化所必需的性质。 具体目标1：使用apoE-KO小鼠动脉粥样硬化模型来验证COG133将调节以下各项的假设： A)血清细胞因子水平：IL-2、IL-4、IL-5、IL-10、IL-12、GM-CSF、干扰素-γ、肿瘤坏死因子-α、IL-6和IL-8 B)血清脂蛋白水平：COG133处理的apoE-KO小鼠的血浆总胆固醇和甘油三酯以及血浆极低密度脂蛋白、低密度脂蛋白、高密度脂蛋白及其各自亚类的数量 C)胸腹主动脉斑块体积 这些第一阶段研究的结果将允许对使用COG133作为一种新型的抗动脉粥样硬化药物的可行性进行初步评估，该药物可以抑制和/或防止导致动脉粥样硬化的免疫功能障碍。Cognosci公司的总体目标是开发一种治疗动脉粥样硬化的新疗法。

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.