Alday P Holland, Doggett Joseph Stone
Division of Infectious Diseases, Oregon Health & Science University.
Division of Infectious Diseases, Oregon Health & Science University; Portland Veterans Affairs Medical Center, Portland, OR, USA.
Drug Des Devel Ther. 2017 Jan 25;11:273-293. doi: 10.2147/DDDT.S60973. eCollection 2017.
causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.
会引发致命和使人衰弱的脑部及眼部疾病。目前用于治疗弓形虫病的药物通常具有毒副作用,且需要持续数周甚至一年以上的长期疗程。治疗时间长以及疾病复发的风险部分归因于对组织囊肿缺乏疗效。开发更有效治疗弓形虫病的挑战包括降低毒性、在脑部和眼部达到治疗浓度、缩短疗程、从宿主体内清除组织囊肿、孕期安全性以及研发一种价格低廉且适用于世界资源匮乏地区的制剂。在过去十年中,在鉴定和开发治疗弓形虫病的新化合物方面取得了重大进展。与用于弓形虫病治疗的临床常用药物不同,这些化合物在临床前开发过程中已针对抗弓形虫病的疗效进行了优化。具有增强疗效以及解决弓形虫病独特方面特征的药物有可能极大地改善弓形虫病的治疗。本综述讨论了与药物设计相关的弓形虫病方面,以及弓形虫病临床前药物研究的进展、挑战和现状。