Drugs in preclinical and early clinical development for the treatment of Chagas´s disease: the current status.

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Fernanda Karoline Vieira da Silva Torchelsen, Ana Lia Mazzeti, Vanessa Carla Furtado Mosqueira
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引用次数: 0

Abstract

Introduction: Chagas disease is spreading faster than expected in different countries, and little progress has been reported in the discovery of new drugs to combat Trypanosoma cruzi infection in humans. Recent clinical trials have ended with small hope. The pathophysiology of this neglected disease and the genetic diversity of parasites are exceptionally complex. The only two drugs available to treat patients are far from being safe, and their efficacy in the chronic phase is still unsatisfactory.

Areas covered: This review offers a comprehensive examination and critical review of data reported in the last 10 years, and it is focused on findings of clinical trials and data acquired in vivo in preclinical studies.

Expert opinion: The in vivo investigations classically in mice and dog models are also challenging and time-consuming to attest cure for infection. Poorly standardized protocols, availability of diagnosis methods and disease progression markers, the use of different T. cruzi strains with variable benznidazole sensitivities, and animals in different acute and chronic phases of infection contribute to it. More synchronized efforts between research groups in this field are required to put in evidence new promising substances, drug combinations, repurposing strategies, and new pharmaceutical formulations to impact the therapy.

用于治疗南美锥虫病的临床前和早期临床开发药物:现状。
导言:恰加斯病在不同国家的传播速度比预期的要快,而在发现抗击克鲁兹锥虫感染的新药方面却进展甚微。最近的临床试验也以希望渺茫而告终。这种被忽视的疾病的病理生理学和寄生虫的遗传多样性异常复杂。仅有的两种可用于治疗患者的药物远非安全,它们在慢性期的疗效仍不令人满意:本综述对过去 10 年中报告的数据进行了全面研究和严格审查,重点关注临床试验结果和临床前研究中获得的体内数据:小鼠和狗模型的活体研究在证明感染治愈方面同样具有挑战性且耗时较长。专家意见:在小鼠和狗模型中进行的活体研究也具有挑战性,而且耗时较长。标准化方案不完善、诊断方法和疾病进展标志物的可用性、使用对苯并咪唑敏感性不同的不同克鲁兹绦虫菌株,以及动物处于不同的急性和慢性感染阶段,都是造成这种情况的原因。这一领域的研究小组之间需要加强合作,以证实新的有前途的物质、药物组合、再利用策略和新的药物制剂,从而对治疗产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
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