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. While there are currently four FDA-approved drugs for AD, they provide only modest symptomatic relief and do not prevent or delay disease. Specifically, in preclinical drug-testing studies, typically performed via in vivo screening of mice, 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. However, currently there are no training opportunities that meet this need by providing the necessary hands-on training. To achieve our goal, we propose to develop and deliver a nationally available, immersion workshop focused on Improving Preclinical Translation of Alzheimer?s Disease Research, to be held at The Jackson Laboratory (JAX) in Bar Harbor, ME. This workshop will leverage the experience and expertise of the Indiana University (IU)/JAX Model Organism Development for Evaluation of Late Onset Alzheimer?s Disease (MODEL-AD) Precision Medicine consortium, including expertise for neuroimaging and clinical pharmacology analytics at IU, and comprehensive skills for in vivo testing at JAX. This training collaboration will convene experts with diverse complementary skills ranging from mouse genetics to statistics to preclinical testing. 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.
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 collaborative research. The workshop will be hosted in the Highseas Conference Center, which provides residential facilities and a state-of-the-art classroom in an informal setting, maximizing the opportunity for participant-faculty interaction. We will also carry out a plan to have appropriate representation of traditionally underrepresented individuals as workshop participants, using well-established mechanisms at JAX and offering partial scholarships. Our innovative and comprehensive workshop will offer a critical, unique training experience that is possible only at JAX.
Given the increasing health and economic burdens associated with the burgeoning number of Alzheimer?s disease (AD) cases throughout the world, there is an urgent need to develop therapeutic agents that can treat, delay, or prevent the disease. However, development of effective new therapies has been hindered by a lack of the skills and knowledge required to perform scientifically rigorous preclinical drug-screening studies, which are typically carried out using laboratory mice. This proposal aims to address these gaps by developing and delivering a workshop at The Jackson Laboratory, a world-renowned center of expertise in the analysis of mice, that will provide participants with hands-on training and lecture instruction that will enable the rigorous design, execution, analysis, and reporting of preclinical experiments that will have potential to bring new AD therapies to the clinic. !
