Development of Apo Mimetic Peptides for the Treatment Cardiovascular Disease

我们之前在动物模型中发现，5A肽可以促进ABCA1转运体的胆固醇外排，减少动脉粥样硬化。在过去的一年里，我们发现这种肽也具有有效的抗炎特性。在与Stew Levine博士的合作中，我们在哮喘小鼠模型中展示了这种肽在减少炎症方面有几种有益的作用。我们最近还发现，在化学诱导的结肠炎小鼠模型中，5A肽也能减少炎症。该肽被授权给KineMed公司，该公司获得了RAID拨款，进行临床前毒理学研究，该研究已经开始。我们还开发了一种基于apoa - 1的最后一个螺旋的新型肽，使用碳氢化合物短链来稳定其形成两亲螺旋的能力。这种新多肽通过ABCA1转运体排出胆固醇的能力优于5A，口服后可减少小鼠动脉粥样硬化。

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.