Development of a mimetic multimodal peptide for the treatment of macular edema

 描述(申请人提供)：黄斑水肿(ME)是继发于视网膜静脉阻塞以及I型和II型糖尿病的一种常见疾病。它是20-74岁人群失明的主要原因。Lucentis和Eylea已被批准用于治疗ME。虽然有效，但对于大约一半的ME患者来说，它们并不能提高视力。我们已经开发出ACX107，这是一种20肽，对一系列促血管生成生长因子具有显著的活性，我们相信它将更有效地改善视力，并在更多的患者中使用，因为它具有广泛的抗血管生成活性。我们发现ACX107能抑制脉络膜新生血管、视网膜新生血管，引起新生血管消退，抑制视网膜脱离，并能显著抑制血管内皮生长因子诱导的血管渗漏。值得注意的是，即使在玻璃体内注射1个月后，这种多肽似乎仍然有效。这些结果提示ACX107有可能成为治疗ME的下一代药物。在这里，我们建议完成剂量范围研究以及活性研究的持续时间，开发一种分析方法来量化ACX107，并进行IND毒理学研究。我们在这里提出的是在第一阶段SBIR机制的预算和时间限制下我们可以完成的全部开发工作的一部分。其余的开发工作将需要更多的资金，我们可以通过第二阶段的SBIR或其他投资，如战略伙伴关系，来实现这一点。

 DESCRIPTION (provided by applicant): Macular edema (ME) is a common disease secondary to retinal vein occlusion and both Type I and Type 2 Diabetes. It is the leading cause of blindness in people between the ages of 20-74. Lucentis and Eylea have been approved for the treatment of ME. Although effective, they do not increase the visual acuity for about half the patients suffering from ME. We have developed ACX107, a 20-mer peptide with remarkable activity against a host of pro-angiogenic growth factors, which we believe will improve vision more effectively and in more patients because of its broad anti-angiogenic activity. We have found that ACX107 inhibits choroidal neovascularization, retinal neovascularization, causes neovascular regression, inhibits retinal detachment, and dramatically inhibits VEGF induced vascular leakage in mouse and rabbit models. Remarkably the peptide appears to work even 1 month after a single intravitreal injection. These results suggest that ACX107 could be the next generation drug for the treatment of ME. Here we propose to complete a dose ranging study as well as a duration of activity study, to develop an analytical method to quantify ACX107, and do IND enabling toxicology studies. What we have proposed here is the portion of the full development work that we can accomplish on the budget and time confines of the Phase I SBIR mechanism. The rest of the development work will require significantly more funding which we could accomplish with a Phase II SBIR or other investment like that of a strategic partnership.