Veterinary and Comparative Neuro-Oncology Laboratory, Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA; Brain Tumor Center of Excellence, Wake Forest University Comprehensive Cancer Center, Medical Center Blvd, NRC 405, Winston Salem, NC, 27157, USA.
Veterinary and Comparative Neuro-Oncology Laboratory, Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA; Brain Tumor Center of Excellence, Wake Forest University Comprehensive Cancer Center, Medical Center Blvd, NRC 405, Winston Salem, NC, 27157, USA.
J Neurosci Methods. 2020 Feb 1;331:108484. doi: 10.1016/j.jneumeth.2019.108484. Epub 2019 Nov 13.
Clinical translation of novel therapeutics that improve the survival and quality of life of patients with neurological disease remains a challenge, with many investigational drug and device candidates failing in advanced stage clinical trials. Naturally occurring inherited and acquired neurological diseases, such as epilepsy, inborn errors of metabolism, brain tumors, spinal cord injury, and stroke occur frequently in companion animals, and many of these share epidemiologic, pathophysiologic and clinical features with their human counterparts. As companion animals have a relatively abbreviated lifespan and genetic background, are immunocompetent, share their environment with human caregivers, and can be clinically managed using techniques and tools similar to those used in humans, they have tremendous potential for increasing the predictive value of preclinical drug and device studies. Here, we review comparative features of spontaneous neurological diseases in companion animals with an emphasis on neuroimaging methods and features, illustrate their historical use in translational studies, and discuss inherent limitations associated with each disease model. Integration of companion animals with naturally occurring disease into preclinical studies can complement and expand the knowledge gained from studies in other animal models, accelerate or improve the manner in which research is translated to the human clinic, and ultimately generate discoveries that will benefit the health of humans and animals.
临床转化新型治疗方法以改善神经疾病患者的生存和生活质量仍然是一个挑战,许多正在研究的药物和设备候选物在后期临床试验中失败。在伴侣动物中经常发生自然发生的遗传性和获得性神经疾病,如癫痫、先天性代谢错误、脑肿瘤、脊髓损伤和中风,许多疾病与人类具有相似的流行病学、病理生理学和临床特征。由于伴侣动物的寿命相对较短,遗传背景简单,免疫功能健全,与人类照顾者共享环境,并且可以使用类似于人类的技术和工具进行临床管理,因此它们在提高临床前药物和设备研究的预测价值方面具有巨大的潜力。在这里,我们回顾了伴侣动物自发性神经疾病的比较特征,重点介绍了神经影像学方法和特征,说明了它们在转化研究中的历史应用,并讨论了每个疾病模型所固有的局限性。将具有自然发生疾病的伴侣动物纳入临床前研究,可以补充和扩展从其他动物模型研究中获得的知识,加速或改善研究向人类临床的转化方式,并最终产生有益于人类和动物健康的发现。