Novel Trypanocidal Compounds for the Treatment of Stage 1 and 2 HAT.

用于治疗 1 期和 2 期 HAT 的新型杀锥虫化合物。

基本信息

批准号：
9046884
负责人：
Harry Ralph Howard
金额：
$ 30万
依托单位：
MEDISYNERGICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-25 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9046884
关键词：
Affect Africa Africa South of the Sahara African Trypanosomiasis Age Arthralgia Blood - brain barrier anatomy Brain Central Africa Cessation of life Chronic Coma Confusion Deterioration Developing Countries Diagnosis Disease Drug Kinetics Eastern Africa Economics Epidemic Evaluation Fever Foundations Goals Headache Health Personnel HepG2 Hour Human Imidazole In Vitro Individual Infection Isomerism Laboratories Lead Libraries Life Style Measurable Measures Modification Neurologic New Agents Organism Parasites Patients Pharmaceutical Preparations Pharmacology Phase Plasma Population Property Pruritus Psyche structure Rattus Research Risk Safety Sleep Sodium Chloride Southern Africa Staging Structure-Activity Relationship Swelling Symptoms Testing Therapeutic Agents Trypanosoma brucei brucei Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense Virulent Western Africa analog base compliance behavior cost disease transmission drug market effective therapy enantiomer improved in vitro Assay in vitro activity in vivo indexing inhibitor/antagonist lymph nodes mouse model novel programs public health relevance receptor screening stereochemistry

项目摘要

DESCRIPTION (provided by applicant): Human African Trypanosomiasis (HAT) is a disease caused by a parasitic organism, trypanosoma brucei. It is often referred to as "sleeping sickness" because of the symptoms that emerge in Stage 2 patients. The disease exists in two forms depending on the causative parasite - Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. T. b. gambiense is found in central and western Africa and causes a chronic condition that can remain in a passive phase for months or more before symptoms emerge. T. b. rhodesiense is found in southern and eastern Africa where symptoms of the infection are more virulent and faster developing than T. b. gambiense. Approximately one-half million inhabitants of sub- Saharan Africa are infected each year by the hemolymphatic, Stage 1, form of HAT. Symptoms include fever, headaches, joint pains and itching and severe swelling of lymph nodes. According to WHO, an estimated 10,000 deaths occurred in 2010 from the neurological, Stage 2, form of HAT. Symptoms are generally more severe, including confusion, reduced coordination and disruption of the sleep cycle, progressive mental deterioration, coma and death. Damage as a result of Stage 2 HAT is irreversible. Only a fraction of all infected patients are adequately treated using available therapeutic agents that are not well tolerated, difficult to administer and costly for patients and health care providers. Newer, more effective treatments, particularly for Stage 2 of the disease, have been lacking. It is the goal of MediSynergics, LLC to discover new agents that will broadly target Stage 1 and Stage 2 HAT infections, with an improved safety and efficacy profile. We have recently identified MS-08 as a novel hit from our compound library that is based on a marketed drug which crosses the blood-brain barrier. It can eliminate Trypanosoma brucei parasites within 72 hours in an in vitro assay. It is expected that any drug which arises from our research will be safe for patients of any age, be conveniently administered orally or intramuscularly on a once daily basis and provide sustained protection at the lowest cost per patient.

描述（由申请人提供）：人类非洲锥虫病 (HAT) 是一种由布氏锥虫引起的疾病，因为该疾病存在于第二阶段，因此通常被称为“昏睡病”。两种形式取决于致病寄生虫 - 布氏冈比亚锥虫或布氏冈比亚锥虫。非洲中部和西部地区，会导致一种慢性疾病，在出现症状之前，该疾病可能会处于被动阶段数月或更长时间，而在南部和东部非洲，其感染症状比 T. b. 更具毒性且发展更快。 b. 撒哈拉以南非洲地区每年约有 50 万居民感染 HAT 第一阶段，症状包括发烧、头痛、关节疼痛、瘙痒和严重肿胀。据世界卫生组织称，2010 年估计有 10,000 人死于神经性 HAT 2 期，症状通常更为严重，包括精神错乱、协调能力下降和睡眠周期中断、进行性精神恶化、昏迷和昏迷。第 2 阶段 HAT 造成的损害是不可逆转的，只有一小部分感染患者能够使用现有的治疗药物进行充分治疗，这些治疗药物耐受性差、难以给药且对患者和医疗保健而言成本高昂。一直缺乏更新、更有效的治疗方法，特别是针对该疾病的第 2 阶段。 MediSynergics, LLC 的目标是发现广泛针对第 1 阶段和第 2 阶段 HAT 感染的新药物，并提高安全性和有效性。我们最近将 MS-08 确定为我们化合物库中的新产品，它基于一种已上市的药物，可在体外 72 小时内消除布氏锥虫寄生虫。预计我们的研究产生的任何药物对于任何年龄的患者都是安全的，可以方便地口服或肌肉注射，每天一次，并以最低的成本为每个患者提供持续的保护。