Vasoactive intestinal peptide for the treatment of psoriasis

描述(申请人提供)：牛皮癣是一种慢性炎症性皮肤病，到目前为止，只有目前可用的治疗方法还不能充分控制这种疾病，这些治疗方法也可能伴随着严重的、有时危及生命的副作用。在这项申请中，我们建议创造一类新的生物制剂药物来治疗这种衰弱的疾病。我们建议将免疫调节神经肽血管活性肠肽(VIP)制成长效制剂，作为治疗银屑病的候选药物进行测试。通过初步实验，我们知道我们的配方可以皮下注射(S.C.)这对患有严重疾病的患者是有利的，我们预计它可以局部应用于不太严重的病例。 在该项目的第一阶段，我们计划合成一批新的药物载体，用于VIP的初步实验。与未配制的VIP相比，该制剂增加了体内半衰期，并提供了更好的安全性能。在拟议的项目中，我们将收集关于VIP在S.C.和局部给药，由于VIP可以降低动脉血压，测量VIP给药后小鼠尾部的血压。S.C.的血压数据已经存在。管理我们的VIP配方。VIP已被证明在许多慢性炎症条件下的动物模型中有效，在这些动物模型中，VIP的疗效与牛皮癣的疗效重叠；然而，它尚未在牛皮癣模型中直接进行测试。因此，我们还建议在本申请中测试我们的长效VIP配方在S.C.在牛皮癣小鼠模型中的给药和局部应用。如果第一阶段成功，我们计划在第二阶段进行正式的毒性研究，进一步开发局部配方，并在第二阶段结束时向FDA提交研究性新药申请。

DESCRIPTION (provided by applicant): Psoriasis is a chronic inflammatory skin disease that to this date is only insufficiently controlled by currently available treatments which can also come with severe, and sometimes life threatening side effects. In this application, we propose to create a new class of biologics drug for the treatment of this debilitating disease. We are proposing to formulate the immunomodulatory neuropeptide vasoactive intestinal peptide (VIP) into a long-acting formulation that will be tested as a drug candidate for the treatment of psoriasis. From preliminary experiments we know that our formulation can be injected subcutaneously (s.c.) which is of advantage for patients with severe disease, and we envision that it can be applied topically for less severe cases. During the Phase I of this project, we propose to synthesize a new batch of drug carrier that we used for the formulation of VIP in preliminary experiments. This formulation has increased in vivo half-life and provides better safety properties compared to unformulated VIP. In the proposed project, we will collect data about bioavailability of VIP after s.c. and topical administration, and, as VIP can decrease the arterial blood pressure, measure the blood pressure in the tail of VIP treated mice after topical administration. Blood pressure data already exists for s.c. administration of our VIP formulation. VIP has been shown to be efficacious in many animal models of chronic inflammatory conditions in which efficacy overlaps with efficacy for psoriasis; however, it has not been tested directly in models of psoriasis. We therefore also propose in this application to test efficacy of our long-acting VIP formulation after s.c. administration and topical application in a mouse model of psoriasis. If Phase I is successful, we are planning to conduct a formal toxicity study during Phase II, further develop the topical formulation and file a investigational new drug application with the FDA at the end of Phase II.