Walter Reed Army Institute for Research, Silver Spring, USA.
London School of Hygiene and Tropical Medicine, London, UK; York Biomedical Research Institute, Department of Biology, University of York, York, UK.
Int J Parasitol Drugs Drug Resist. 2019 Dec;11:106-117. doi: 10.1016/j.ijpddr.2019.06.003. Epub 2019 Jun 20.
Although there have been significant advances in the treatment of visceral leishmaniasis (VL) and several novel compounds are currently in pre-clinical and clinical development for this manifestation of leishmaniasis, there have been limited advances in drug research and development (R & D) for cutaneous leishmaniasis (CL). Here we review the need for new treatments for CL, describe in vitro and in vivo assays, models and approaches taken over the past decade to establish a pathway for the discovery, and pre-clinical development of new drugs for CL. These recent advances include novel mouse models of infection using bioluminescent Leishmania, the introduction of PK/PD approaches to skin infection, and defined pre-clinical candidate profiles.
尽管内脏利什曼病(VL)的治疗取得了重大进展,并且目前有几种新型化合物正在临床前和临床开发中用于治疗这种利什曼病的表现形式,但皮肤利什曼病(CL)的药物研究和开发(R&D)进展有限。在这里,我们回顾了对 CL 的新疗法的需求,描述了过去十年中为发现和 CL 的新药的临床前开发而建立的体外和体内检测、模型和方法。这些最新进展包括使用生物发光利什曼菌的新型感染小鼠模型,引入了皮肤感染的 PK / PD 方法以及明确的临床前候选物特征。