Adoption of a mouse model of veterinary filariasis for preclinical drug testing

心虫是猫、狗和雪貂同伴动物的一种潜在威胁生命的传染病，也可能对意外感染的人的眼睛和肺部造成损害。心线虫是一个全球性的兽医问题，由于气候变化，它正在美国和欧洲蔓延。每年有高达4亿美元的资金被花在治疗上，以阻止宠物感染心线虫。由于抗药性寄生虫的出现，我们需要开发和测试新的药物疗法。药物测试是在实验室饲养的猫或狗身上进行的，这些猫或狗实验上感染了心虫。我们估计每年至少有221只猫狗被用于这一目的。这些主要是长期实验，存在因慢性蠕虫感染心脏和肺而造成严重损害的风险。我们建立了一种新的心虫性小鼠模型。这个模型模拟了猫和狗感染的早期阶段，在它们迁移到心脏导致疾病之前，微小的幼虫在皮肤下生长。我们已经在这个小鼠模型中测试了目前的心虫药物，也在清除发育中的寄生虫并在体外孵化它们之后进行了测试。我们已经确定这些模型可以成功地用于评估新药。在这个项目中，我们将把新的幼虫心虫小鼠模型转移到两个主要的最终用户组织，这两个组织在过去三年中参与了大约一半的已发表的心线虫药物研究。我们将与我们的最终用户合作伙伴共享方案并进行实验，以评估该模型在这些机构中作为衡量抗心虫药物反应的一种方式的效果如何。然后，我们将通过免费获取出版物、通过将方法和结果发布在全球许多心线虫研究人员访问的网站上以及通过在有主要利益相关者(如学者、我们估计，未来采用新的心线虫小鼠模型来测试药物，可以减少目前使用的猫狗的三分之二，从而减少这些特殊保护物种遭受痛苦的程序总数。

Heartworm is a potentially life-threatening infectious disease of cats, dogs and ferret companion animals and also can cause damage to the eyes and lungs of people who are accidentally infected. Heartworm is a global veterinary problem and is spreading across America and Europe due to climate change. As much as 400 million dollars are spent every year on treatments to stop heartworm infections in pets. Because of the emergence of drug resistant parasites, we need to develop and test new drug therapies. Drug testing is done on laboratory bred cats or dogs experimentally infected with heartworm. We estimate that at least 221 cats and dogs are utilised for this purpose yearly. These are mainly long-term experiments with a risk of severe harm occurring due to chronic worm infections of the heart and lungs. We have established a new mouse model of heartworm. This model mimics the early stages of infections in cats and dogs with microscopic larvae growing under the skin, before they migrate to the heart to cause disease. We have tested current heartworm drugs in this mouse model and also after removing the developing parasites and incubating them outside of the body. We have determined that these models can be used to successfully evaluate new drugs.In this project, we will transfer the new larval heartworm mouse model to two major end-user organisations who have been involved in approximately half of all published research on heartworm drugs over the last three years. With our end-user partners we will share protocols and undertake experiments to evaluate how well the model works in these establishments as a way of measuring anti-heartworm drug responses.We will then share our protocols and findings by free to access publication, by posting methods and results on a website accessed by many heartworm researchers worldwide and by running a workshop at a major heartworm meeting attended by major stakeholders such as academics, practitioners and representatives of the animal healthcare industry.We estimate that the future adoption of the new mouse model of heartworm to test drugs could reduce up to two-thirds of the cats and dogs currently used and thus also reduce the total numbers of procedures causing suffering in these specially-protected species.