Vasoactive intestinal peptide for the treatment of psoriasis

血管活性肠肽治疗牛皮癣

基本信息

批准号：
8248548
负责人：
Elijah M. Bolotin
金额：
$ 22.68万
依托单位：
PHARMAIN CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-07 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8248548
关键词：
Adverse effects Affect Animal Model Antigens Area Autoimmunity Binding Biological Availability Biological Response Modifier Therapy Blood Blood Pressure Body Surface Calculi Chronic Crohn&apos s disease Data Disease Dose Drops Drug Carriers Drug Delivery Systems Drug Formulations Elbow Excretory function Friction Half-Life Human Hypersensitivity Immune System Diseases Immunosuppression In Vitro Infection Inflammatory Insulin-Dependent Diabetes Mellitus Investigational New Drug Application Kidney Lead Life Malignant Neoplasms Measures Medical Mental Depression Modeling Multiple Sclerosis Mus NIH Program Announcements National Institute of Allergy and Infectious Disease Neuropeptides Ointments Patients Peptide Hydrolases Peptides Pharmaceutical Preparations Phase Preparation Property Psoriasis Psoriatic Arthritis Quality Control Quality of life Rheumatoid Arthritis Risk Route Safety Skin Small Business Innovation Research Grant Subcutaneous Injections Tail Technology Testing Therapeutic Topical application Toxic effect Transplantation Vaccines Vasoactive Intestinal Peptide Work base copolymer cytokine drug candidate efficacy testing in vivo mouse model nanocarrier novel research study response self esteem skin disorder success

项目摘要

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.

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，仅通过当前可用的治疗方法来控制，这也可能带来严重的副作用，有时还会带来严重的副作用。在此应用中，我们建议创建一种新的生物制剂来治疗这种使人衰弱的疾病。我们提议制定免疫调节性神经肽血管活性肠肽（VIP）为长效制剂，该制剂将作为治疗牛皮癣治疗的药物进行测试。从初步实验中，我们知道可以皮下注射我们的配方（S.C.），这对患有严重疾病的患者有优势，并且我们设想可以局部应用它适用于不太严重的病例。在该项目的第一阶段，我们建议合成一批新的药物载体，用于初步实验中的VIP制定。与未构造的VIP相比，该公式在体内半衰期增加了，并提供了更好的安全性能。在拟议的项目中，我们将收集有关S.C.之后VIP生物利用度的数据。和局部给药，并且由于VIP可以降低动脉血压，因此在局部给药后测量了VIP处理的小鼠尾部的血压。 S.C.已经存在血压数据管理我们的VIP配方。在许多慢性炎症条件下的动物模型中，VIP已被证明是有效的，在这些动物模型中，疗效与牛皮癣有效性重叠。但是，尚未直接在牛皮癣模型中进行测试。因此，我们还建议在此应用中测试S.C.之后的长效VIP公式的功效。在牛皮癣的小鼠模型中给药和局部应用。如果第一阶段成功，我们正计划在II期期间进行正式的毒性研究，进一步开发局部配方，并在II期结束时向FDA提交研究性新药物应用。公共卫生相关性：牛皮癣是一种使人衰弱的慢性炎症性皮肤状况，对经济负担很大，尽管有疗法的进步，但仍然是很大程度上无法满足的医疗需求。该建议将创建一种新的生物制剂，可以通过皮下注射和不太严重的局部应用来施用，其可能会改变患者的生活。