Improving Preclinical Translation in Alzheimer's Disease Research

项目总结/文摘

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.