Improving Preclinical Translation in Alzheimer's Disease Research

项目总结/摘要 我们的长期目标是确保严格的、最佳实践的科学方法始终适用于 这些实验为阿尔茨海默病（AD）的潜在疗法产生临床前数据。AD数量 全球病例急剧增加，迫切需要开发有效的新疗法， 目前FDA批准的治疗AD的药物的适度疗效。鉴于临床前药物筛选的数据 在动物模型中用于告知AD患者的临床试验，确保最高水平的严格性至关重要 并保证从动物模型到人类患者的成功转化。不幸的是，在临床前 药物测试研究，有证据表明，在实验设计，样本量，数据分析， 药物筛选管道的优化，以及个人生成数据的经验，共同表明 需要更好地培训临床前药物发现和转化医学方法和流程。 在过去的三年里，我们成功地提供了一个年度课程，通过提供 必要的实践以及理论培训的基本技能所需的进行严格的， AD小鼠模型的体内研究。在此，我们建议继续提供这种全国可用的沉浸式 研讨会的重点是改善阿尔茨海默病临床前翻译的原则和技术 研究，将在位于缅因州巴尔港的杰克逊实验室（JAX）举行，该实验室将利用 印第安纳州大学（IU）/JAX/匹兹堡大学（PITT）用于评价晚期 发病阿尔茨海默病（模型-AD）财团。这次培训合作将召集专家， 从小鼠遗传学到统计学，再到最先进的临床前测试， 住宅会议中心和JAX的小鼠动手训练设施。该研讨会将确保一个多样化的 各专业职等的群体，并使传统上任职人数偏低的群体有适当的代表性 个人作为讲习班参与者，并得到奖学金的支持。根据NIH关于严谨性的倡议， 重现性，研讨会旨在解决培训差距，在临床前药物筛选，提供参与者 具有严格设计、执行、分析和报告药代动力学所需的技能和知识， 药效学和临床前功效实验。该研讨会的创新之处在于，它包括一个 在体内药物筛选方法方面进行大量的动手实践实验室培训。具体 研讨会的目的是1）培训参与者严格的设计，实验执行，分析， 根据ARRIVE AD治疗临床前试验指南报告数据。2)为参与者提供 具有实用的实验室工具和技能，可在小鼠模型上进行严格的，可重复的临床前试验 的AD。3)促进教师和学生之间的互动和讨论，以促进开放，诚实的对话， 跨参与者背景多样性的合作研究。我们的创新和全面 研讨会将提供一个关键的，独特的动手培训经验，这是可能只有在JAX。

PROJECT SUMMARY/ABSTRACT Our long-term goal is to ensure that rigorous, best-practice scientific methods are consistently applied in experiments generating preclinical data for potential therapies for Alzheimer’s disease (AD). The number of AD cases is rising dramatically worldwide, and there is an urgent need to develop effective new therapies beyond the modest efficacy of the current FDA approved drugs for AD. Given that data from preclinical drug screening in animal models are used to inform clinical trials in AD patients, it is critical to ensure the highest level of rigor and assurances for successful translation from animal models to human patients. Unfortunately, in preclinical drug testing studies, there has been evidence of deficiencies in experimental design, sample size, data analysis, optimization of drug screening pipelines, and experience of individuals generating the data, together indicating a need for better training in preclinical drug discovery and translational medicine methodologies and processes. Over the last three years we have successfully delivered an annual course that meets this need by providing the necessary hands-on as well as theoretical training in fundamental skillsets required for conducting rigorous in vivo studies in AD mouse models. Herein we propose to continue providing this nationally available, immersion workshop focused on Principles and Techniques for Improving Preclinical Translation of Alzheimer’s Disease Research, to be held at The Jackson Laboratory (JAX) in Bar Harbor, ME that will leverage the expertise of the Indiana University (IU)/JAX/University of Pittsburgh (PITT) Model Organism Development for Evaluation of Late Onset Alzheimer’s Disease (MODEL-AD) consortium. This training collaboration will convene experts with diverse complementary skills ranging from mouse genetics to statistics to preclinical testing at a state-of-the-art residential conference center and hands-on training facility for mice at JAX. The workshop will ensure a diverse group across professional levels and have appropriate representation of traditionally underrepresented individuals as workshop participants, and supported by scholarships. In line with the NIH initiative on rigor and reproducibility, the workshop aims to address training gaps in preclinical drug screening by providing participants with the skills and knowledge required for rigorous design, execution, analysis, and reporting of pharmacokinetic, pharmacodynamics, and preclinical efficacy experiments. The workshop is innovative in that it includes a significant amount of hands-on, practical laboratory training in in vivo drug screening methodologies. The specific aims of the workshop are to 1) Train participants in the rigorous design, experimental execution, analysis, and reporting of data in line with the ARRIVE guidelines for preclinical testing of AD therapies. 2) Provide participants with the practical laboratory tools and skills to perform rigorous, reproducible preclinical tests on mouse models of AD. 3) Promote interaction and discussion between faculty and students to foster open, honest dialogue and collaborative research across a diversity of participant backgrounds. Our innovative and comprehensive workshop will offer a critical, unique hands-on training experience that is possible only at JAX.