Development of Apo Mimetic Peptides for the Treatment Cardiovascular Disease

用于治疗心血管疾病的 Apo 模拟肽的开发

• 批准号: 8558035
• 负责人: Alan Thomas Remaley
• 金额: $ 66.32万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8558035
• 关键词: Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antiatherogenic; Apolipoprotein A-I; Apolipoproteins; Asthma; Atherosclerosis; Biological; Cardiovascular Diseases; Chemicals; Cholesterol; Clinical Trials; Colitis; Collaborations; Development; Goals; Grant; High Density Lipoproteins; Hydrocarbons; Inflammation; Infusion procedures; Licensing; Mus; Peptides; Property; Structural Protein; Therapeutic Agents; Toxicology; base; mimetics; mouse model; novel; particle; pre-clinical

We previously showed that the 5A peptide can promote cholesterol efflux by the ABCA1 transporter and reduce atherosclerosis in animal models. In the past year, we showed that the peptide also has potent anti-inflammatory properties. In collaboration, with Dr. Stew Levine, we showed that the peptide had several beneficial effects in reducing inflammation in a mouse model of asthma. We recently have also shown that the 5A peptide also reduces inflammation in a chemical induced mouse model of colitis. The peptide was licensed to KineMed Inc, who received a RAID grant for performing preclinical toxicology studies, which have commenced. We have also developed a novel peptide based on last helix of apoA-I, using a hydrocarbon staple to stabilize its ability to form an amphipathic helix. The new peptide was superior to 5A in terms of its potency for effluxing cholesterol by the ABCA1 transporter and it reduced atherosclerosis in mice when given orally.

我们先前表明，5A肽可以促进ABCA1转运蛋白的胆固醇外排，并减少动物模型中的动脉粥样硬化。 在过去的一年中，我们表明该肽还具有有效的抗炎特性。与Stew Levine博士合作，我们表明该肽在减少哮喘小鼠模型中的炎症方面具有几种有益的作用。 我们最近还表明，5A肽还减少了化学诱导的结肠炎模型中的炎症。 该肽获得了Kinemed Inc的许可，Kinemed Inc获得了促进临床前毒理学研究的突袭赠款。 我们还使用碳氢化合物的主食来稳定其形成两亲性螺旋的能力。 就其通过ABCA1转运蛋白排出胆固醇的效力而言，新的肽优于5A，并且在口服口服时会降低小鼠的动脉粥样硬化。