检测血液中的抗原以评估治疗效果和在恰加斯病小鼠模型中的治愈情况。
antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease.
机构信息
Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil.
Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
出版信息
Front Immunol. 2024 Jan 12;14:1340755. doi: 10.3389/fimmu.2023.1340755. eCollection 2023.
INTRODUCTION
Chagas disease (CD) is caused by the protozoan parasite . Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays for drug discovery are required to accelerate the development of new drugs with reduced side effects, which are much needed for human treatment.
METHODS
We used a cure model of infected mice treated with Fexinidazole (FZ) to further validate a novel Enzyme Linked Aptamer (ELA) assay that detects parasite biomarkers circulating in the blood of infected animals.
RESULTS
The ELA assay showed cure by FZ in ~71% and ~77% of mice infected with the VL-10 and Colombiana strains of , respectively. The ELA assay also revealed superior treatment efficacy of FZ compared to Benznidazole prior to immunosuppression treatment.
DISCUSSION
Our study supports the use of ELA assay as an alternative to traditional serology or blood PCR to assess the efficacy of antichagasic drugs during their preclinical phase of development. Further, the combination of high sensitivity and ease of use make this parasite antigen detection assay an attractive new tool to facilitate the development of much needed new therapies for CD.
简介
恰加斯病（CD）是由原生动物寄生虫引起的。尽管该病主要流行于拉丁美洲，但由于感染个体向非流行地区的迁移，CD 已成为全球公共卫生问题。尽管在药物开发方面取得了进展，但仍需要进行临床前药物发现检测，以加速开发具有较少副作用的新药，这对人类治疗非常重要。
方法
我们使用感染小鼠的治愈模型，用非达唑胺（FZ）进行治疗，进一步验证了一种新型酶联适体（ELA）检测法，该方法可检测感染动物血液中循环的寄生虫生物标志物。
结果
ELA 检测法显示，VL-10 和 Colombiana 株分别有约 71%和 77%的感染小鼠被 FZ 治愈。ELA 检测法还显示，在进行免疫抑制治疗之前，FZ 的治疗效果优于苯硝唑。
讨论
我们的研究支持在药物开发的临床前阶段，使用 ELA 检测法替代传统的血清学或血液 PCR 来评估抗恰加斯病药物的疗效。此外，该寄生虫抗原检测法具有高灵敏度和易用性的特点，是一种有吸引力的新工具，可以促进急需的 CD 新疗法的开发。
Zotero 插件