Vasoactive intestinal peptide for the treatment of psoriasis

描述（由申请人提供）：牛皮癣是一种慢性炎症性皮肤病，到目前为止，现有的治疗方法还不能充分控制牛皮癣，而且牛皮癣还会带来严重的，有时甚至危及生命的副作用。在这个申请中，我们建议创建一类新的生物制剂药物来治疗这种使人衰弱的疾病。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，作为治疗牛皮癣的候选药物进行试验。从初步的实验中，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来说是有利的，我们设想它可以局部应用于不太严重的病例。

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. PUBLIC HEALTH RELEVANCE: Psoriasis is a debilitating chronic inflammatory skin condition with an immense burden on the economy and, despite treatments advances, is still a largely unmet medical need. This proposal would create a new class of biologics drug that can be administered both by subcutaneous injection and for less severe cases by topical application that has the potential of changing the lives of the patients.