Novel COG Compounds to Treat Asthma

描述（由申请人提供）：我们的总体目标是销售一种COG化合物(又名。apoe -拟态肽)用于治疗哮喘患者。Cognosci已经发现了一系列新的COG化合物，这些化合物是载脂蛋白e的功能模拟物，并获得了专利。这些COG化合物在多种基于细胞和基于动物的人类疾病条件模型中具有深刻的抗炎活性（Vitek等人，2011，Christensen等人，2011，Li等人，2008，Lynch等人，2003等）。COG化合物在小鼠，大鼠和狗身上的耐受性也非常好，在长达90天的测试中，每天重复给药。在一篇完全出乎意料的论文中，Levine和他在美国国家心肺血液研究所（NHLBI）的同事独立发现apoE-130-149在尘螨诱导的哮喘小鼠模型中显著降低了哮喘的体征、症状和特征。ApoE-130-149被我们称为COG130，是一种由Cognosci拥有的专利物质组合物。这些事件现在使我们处于一个独特的位置，以验证和扩展Levine在第一阶段提案中的开创性工作，以便我们可以：1)证明COG130可以有效地雾化成气溶胶，并且吸入的气溶胶在小鼠单次和重复给药时具有良好的耐受性；2)吸入COG130在室内尘螨诱导的小鼠哮喘模型中产生剂量依赖性的哮喘特征减少。本提案中实验工作计划的成功完成所产生的数据将为Cognosci充分开发将COG化合物用于治疗哮喘的临床应用所需的医学、商业和监管要求奠定基础。

DESCRIPTION (provided by applicant): Our overall goal is to market a COG compound (aka. apoE-mimetic peptides) for the treatment of patients with asthma. Cognosci has discovered, patented and published a novel series of COG compounds which are functional mimetics of apolipoprotein-E. These COG compounds have profound anti-inflammatory activities in a wide variety of cell-based and animal-based models of human disease conditions (Vitek et al. 2011, Christensen et al. 2011, Li et al. 2008, Lynch et al. 2003, and others). The COG compounds are also extremely well tolerated in mice, rats and dogs following repeated daily dosing for as many as 90 days that was tested. In a totally unanticipated publication, Levine and colleagues at National Institutes of Heart, Lung and Blood (NHLBI) independently found that apoE-130-149 significantly reduced the signs, symptoms and characteristics of asthma in a house dust mite-induced model of asthma in mice. ApoE-130-149 is known to us as COG130, a patented composition of matter owned by Cognosci. These events have now put us in a unique position to verify and extend Levine's pioneering work in this Phase I proposal so that we can: 1) show that COG130 can be efficiently nebulized into an aerosol, and that the inhaled aerosol is well tolerated in single and repeat dosing in mice and 2) that inhaled COG130 produces a dose-dependent reduction of asthmatic characteristics in a House Dust Mite-induced model of asthma in mice. The data generated from the successful completion of the experimental work plan in this proposal will lay the foundation for the medical, commercial and regulatory requirements that Cognosci will need to fully develop to move a COG compound into clinical use for the treatment of asthma. PUBLIC HEALTH RELEVANCE: Asthma is a highly prevalent disease affecting 300 million patients worldwide, with 24 million in the United States including 10 million children, and its numbers appear to be increasing. Sadly, in spite of our best efforts to provide medical care, 5000 asthmatic patients die each year from their disease (about 100 per week). Clearly we need new and more effective treatments to control asthma, particularly severe asthma that includes acute life-threatening situations. This proposal is to test a totally novel approach, where COG compounds, which are peptide mimetics of apolipoprotein-E, confer profound anti-inflammatory activity, reduce airway hyperresponsiveness and reduce airway remodeling that is associated with the asthmatic condition in mouse models. Based on the data collected in these proposed studies, we will be able to define how COG130 aerosols are tolerated in healthy mice and how they can reduce the signs and symptoms of disease in a house dust mite-induced model of asthma in mice. These studies are part of the foundation that we need to build to complete FDA required safety and toleratiblity studies in animals as a prelude to clinical testing in human asthmatic patients.