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治疗恰加斯病的新方法。

New Approaches for the Treatment of Chagas Disease.

机构信息

Centre for Drug Design Discovery and Development (C4D), SRM University, DelhiNCR, Rajiv Gandhi Education City, Sonepat - 131 029, Haryana, India.

Laboratorio de Imunologia, Instituto do Coracao, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.

出版信息

Curr Drug Targets. 2021;22(7):835-841. doi: 10.2174/1389450121999201124122643.

Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi is a neglected tropical disease with high prevalence (5.7 million in Latin America, WHO 2015), significant burden, and significant morbimortality mostly due to severe heart disorders during the chronic phase of infection. Chagas disease is endemic in Latin America, and medical care for the disease is the major expense for Brazil's Universal Healthcare System (Sistema Único de Saúde (SUS). The efficacy of the available drugs benznidazole and nifurtimox are low for the chronic phase of Chagas disease, the phase in which most patients are diagnosed, and there are frequent side effects, and drug resistance occurs. The rapid deployment of new drug regimens that are effective for the chronic phase treatment is low-cost and less toxic than the currently available therapy, which is a global priority. Repurposing drugs already in clinical use with other combinations would be the fastest and safest strategy for treating Chagas disease patients. We hypothesize that the combined treatment using repurposing drugs with benznidazole will be more efficacious than benznidazole alone. This needs to be tested further both in vitro and in animal models to understand the efficacy of the treatment before performing human clinical trials. We further hypothesize that producing nanoparticle formulation of the drugs can reduce their toxicity and improve therapeutic use.

摘要

恰加斯病由原生动物克氏锥虫引起,是一种被忽视的热带病,在拉丁美洲的患病率很高(世界卫生组织 2015 年为 570 万),负担沉重,发病率和死亡率高,主要是由于感染的慢性期出现严重的心脏疾病。恰加斯病在拉丁美洲流行,该病的医疗费用是巴西全民医疗保健系统(Sistema Único de Saúde (SUS) 的主要支出。现有的苯并咪唑和硝呋替莫治疗恰加斯病慢性期的疗效较低,而大多数患者都是在这个阶段被诊断出来的,而且这些药物还存在频繁的副作用和耐药性问题。快速部署针对慢性期的新药物方案,具有成本效益且毒性低于现有的治疗方法,这是全球的优先事项。重新利用已经在临床使用的药物与其他药物联合使用,将是治疗恰加斯病患者最快和最安全的策略。我们假设使用重新利用的药物与苯并咪唑联合治疗将比单独使用苯并咪唑更有效。这需要在体外和动物模型中进一步测试,以了解治疗的疗效,然后再进行人体临床试验。我们进一步假设,生产这些药物的纳米颗粒制剂可以降低其毒性并改善治疗用途。

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