Robarts Research Institute, The University of Western Ontario, Ontario, Canada; Department of Physiology and Pharmacology, The University of Western Ontario, Ontario, Canada.
Robarts Research Institute, The University of Western Ontario, Ontario, Canada; BrainsCAN, The University of Western Ontario, Ontario, Canada.
Neurobiol Learn Mem. 2021 Jul;182:107443. doi: 10.1016/j.nlm.2021.107443. Epub 2021 Apr 22.
Translating results from pre-clinical animal studies to successful human clinical trials in neurodegenerative and neuropsychiatric disease presents a significant challenge. While this issue is clearly multifaceted, the lack of reproducibility and poor translational validity of many paradigms used to assess cognition in animal models are central contributors to this challenge. Computer-automated cognitive test batteries have the potential to substantially improve translation between pre-clinical studies and clinical trials by increasing both reproducibility and translational validity. Given the structured nature of data output, computer-automated tests also lend themselves to increased data sharing and other open science good practices. Over the past two decades, computer automated, touchscreen-based cognitive testing methods have been developed for non-human primate and rodent models. These automated methods lend themselves to increased standardization, hence reproducibility, and have become increasingly important for the elucidation of the neurobiological basis of cognition in animal models. More recently, there have been increased efforts to use these methods to enhance translational validity by developing task batteries that are nearly identical across different species via forward (i.e., translating animal tasks to humans) and reverse (i.e., translating human tasks to animals) translation. An additional benefit of the touchscreen approach is that a cross-species cognitive test battery makes it possible to implement co-clinical trials-an approach developed initially in cancer research-for novel treatments for neurodegenerative disorders. Co-clinical trials bring together pre-clinical and early clinical studies, which facilitates testing of novel treatments in mouse models with underlying genetic or other changes, and can help to stratify patients on the basis of genetic, molecular, or cognitive criteria. This approach can help to determine which patients should be enrolled in specific clinical trials and can facilitate repositioning and/or repurposing of previously approved drugs. This has the potential to mitigate the resources required to study treatment responses in large numbers of human patients.
将临床前动物研究的结果转化为神经退行性和神经精神疾病的成功人体临床试验是一个重大挑战。虽然这个问题显然是多方面的，但用于评估动物模型认知的许多范式的可重复性和较差的转化有效性是导致这一挑战的核心因素。计算机自动化认知测试组合有可能通过提高可重复性和转化有效性，大大促进临床前研究与临床试验之间的转化。鉴于数据输出的结构化性质，计算机自动化测试也有利于增加数据共享和其他开放科学的良好实践。在过去的二十年中，已经为非人类灵长类动物和啮齿动物模型开发了基于计算机自动化、触摸屏的认知测试方法。这些自动化方法有助于提高标准化程度，从而提高可重复性，并且对于阐明动物模型认知的神经生物学基础变得越来越重要。最近，人们越来越努力地通过开发几乎在不同物种中都相同的任务组合来使用这些方法来提高转化有效性，这些任务组合是通过正向（即，将动物任务转化为人类）和反向（即，将人类任务转化为动物）翻译实现的。触摸屏方法的另一个好处是，跨物种认知测试组合使得实施共临床试验成为可能，这种方法最初是在癌症研究中开发的，用于神经退行性疾病的新治疗方法。共临床试验将临床前和早期临床试验结合在一起，有利于在具有潜在遗传或其他变化的小鼠模型中测试新的治疗方法，并可以帮助根据遗传、分子或认知标准对患者进行分层。这种方法可以帮助确定哪些患者应该被纳入特定的临床试验，并有助于重新定位和/或重新利用以前批准的药物。这有可能减少研究大量人类患者治疗反应所需的资源。
