Topical Drug Treatment of Cutaneous Leishmaniasis

皮肤利什曼病的局部药物治疗

基本信息

批准号：
9383791
负责人：
Brian David Gray
金额：
$ 21.42万
依托单位：
MOLECULAR TARGETING TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9383791
关键词：
Acetates Address Adverse effects Aftercare Animal Model Anions Area Biodistribution Biological Assay Blood Circulation Cessation of life Chemicals Clinical Complex Cutaneous Cutaneous Leishmaniasis Data Dermal Development Disease Drug Industry Economics Elements Ethanol Excipients Exhibits FDA approved Female Fluorescence Formulation Gel Goals HIV Harvest Housing Human Image Immune system In Vitro Inbred BALB C Mice Incentives Infection International Health Problems Investments Irritants Leishmania Leishmania major Leishmaniasis Lesion Malnutrition Measures Methods Molecular Target Monitor Morbidity - disease rate Mus Necrosis Nitrates Octanols Ointments Organ Parasites Permeability Pharmaceutical Preparations Pharmacologic Substance Pharmacotherapy Phase Polyethylene Glycols Poverty Property Propylene Glycols Proteins Protozoa Reporting Resistance Resources Risk Sampling Sex Discrimination Skin Skin Ulcer Slice Small Business Innovation Research Grant Stains Structure Technology Testing Tissue Viability Tissues Topical application Toxic effect Toxicology Universities Vaccination Visceral World Health Organization Zinc chemotherapy clinical translation clinically relevant co-infection cohort drug development drug discovery expectation experimental study histological stains illiteracy in vivo Model mortality mouse model new technology novel skin irritation skin lesion standard measure standard of care vector control

项目摘要

Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a disease that is characterized by a spectrum of clinical manifestations ranging from ulcerative skin lesions to fatal visceral infections. Leishmaniasis is a poverty-related disease and is associated with malnutrition, displacement, poor housing, illiteracy, gender discrimination, weakness of the immune system and lack of resources. Leishmaniasis is further compromised by the emergence of co-infection with human immunodeficiency virus (HIV) in endemic areas. Globally, there are an estimated 1.5–2 million new cases of leishmaniasis and 80,000 deaths each year, and 350 million people are at risk of infection and disease. In the absence of vaccination, chemotherapy, together with vector control, remains one of the most important elements in the control of leishmaniasis. However, this strategy is seriously threatened by the high toxicity of clinical drugs and the rampant increase of resistance in the field. As leishmaniasis is a disease of poverty, pharmaceutical companies have had limited incentive for the search of novel anti-leishmanial drugs because there would be low economic return on their investment. The goal of this SBIR application is to develop an affordable and effective antileishmanial ointment for treating cutaneous leishmaniasis (CL) in both developed and developing areas of the world. Our team recently discovered that zinc(II)-dipicolylamine (ZnDPA) complexes have strong antileishmanial activity against Leishmania major one of the causative agents of CL. Molecular Targeting Technologies Inc. will develop ointment formulations of ZnDPA and the team at the University of Notre Dame will test these ointments in an in vivo model of CL that takes advantage of a genetically modified L. major strain which stably express a red fluorescent mCherry protein. Furthermore, the proposed studies on skin toxicity and biodistribution of ZnDPA will be significant for a successful clinical translation.

利什曼原虫属的原生动物寄生虫是利什曼病属，一种疾病其特征是一系列临床表现，从溃疡性皮肤病变到致命内脏感染。利什曼病是一种与贫困有关的疾病，与营养不良有关，流离失所，住房不良，文盲，性别歧视，免疫系统的弱点和缺乏资源。与人类共同感染的出现，利什曼病进一步损害了内在区域的免疫缺陷病毒（HIV）。在全球范围内，估计有15-20万个新案件利什曼病和每年80,000人死亡，3.5亿人有感染和疾病的风险。缺乏疫苗，化疗以及载体控制仍然是最重要的利什曼病控制中的元素。但是，这种策略受到高毒性的严重威胁临床药物和该野外抵抗力的猖ramp。因为利什曼病是一种疾病贫困，制药公司对搜索新型抗leshmanial药物的诱因有限因为他们的投资经济回报率低。该SBIR应用的目的是开发一种负担得起有效的反抗抗精剂软膏在世界发达和发展中的皮肤利什曼病（CL）治疗皮肤利什曼病（CL）。我们的团队最近发现锌（II） - 二吡咯胺（ZnDPA）复合物具有强大的抗抗精度活性反对利什曼原虫的主要因果因素。分子靶向技术公司将 ZnDPA的开发软膏公式和巴黎大学的团队将测试这些在CL的体内模型中的药膏，它利用了一般修饰的L.主要菌株的优势静态表达红色荧光麦克利蛋白。此外，提议的关于皮肤毒性和对于成功的临床翻译，ZnDPA的生物分布将很重要。