Hemphill Andrew, Stadelmann Britta, Rufener Reto, Spiliotis Markus, Boubaker Ghalia, Müller Joachim, Müller Norbert, Gorgas Daniela, Gottstein Bruno
Vetsuisse Faculty, Institute of Parasitology, University of Berne, Länggass-Strasse 122, 3012 Berne, Switzerland.
Department of Clinical Veterinary Medicine, Clinical Radiology, Bremgartenstrasse 109a, 3012 Berne, Switzerland.
Parasite. 2014;21:70. doi: 10.1051/parasite/2014073. Epub 2014 Dec 22.
The search for novel therapeutic options to cure alveolar echinococcosis (AE), due to the metacestode of Echinococcus multilocularis, is ongoing, and these developments could also have a profound impact on the treatment of cystic echinococcosis (CE), caused by the closely related Echinococcus granulosus s.l. Several options are being explored. A viable strategy for the identification of novel chemotherapeutically valuable compounds includes whole-organism drug screening, employing large-scale in vitro metacestode cultures and, upon identification of promising compounds, verification of drug efficacy in small laboratory animals. Clearly, the current focus is targeted towards broad-spectrum anti-parasitic or anti-cancer drugs and compound classes that are already marketed, or that are in development for other applications. The availability of comprehensive Echinococcus genome information and gene expression data, as well as significant progress on the molecular level, has now opened the door for a more targeted drug discovery approach, which allows exploitation of defined pathways and enzymes that are essential for the parasite. In addition, current in vitro and in vivo models that are used to assess drug efficacy should be optimized and complemented by methods that give more detailed information on the host-parasite interactions that occur during drug treatments. The key to success is to identify, target and exploit those parasite molecules that orchestrate activities essential to parasite survival.
由于多房棘球绦虫的中绦期幼虫引发的泡型包虫病(AE),目前正在寻找新的治疗方法,这些进展也可能对由密切相关的细粒棘球绦虫复合种引起的囊型包虫病(CE)的治疗产生深远影响。目前正在探索多种选择。鉴定具有化学治疗价值的新化合物的一个可行策略包括全生物体药物筛选,采用大规模体外中绦期幼虫培养,并且在鉴定出有前景的化合物后,在小型实验动物中验证药物疗效。显然,当前的重点是针对已上市或正在开发用于其他用途的广谱抗寄生虫或抗癌药物及化合物类别。多房棘球绦虫完整基因组信息和基因表达数据的可用性,以及分子水平上的重大进展,现在为更具针对性的药物发现方法打开了大门,这种方法可以利用对寄生虫至关重要的特定途径和酶。此外,目前用于评估药物疗效的体外和体内模型应进行优化,并辅以能提供药物治疗期间宿主与寄生虫相互作用更详细信息的方法。成功的关键是识别、靶向并利用那些协调对寄生虫生存至关重要的活动的寄生虫分子。