Open Drug Discovery Center for Alzheimer's Disease

阿尔茨海默病（AD）迫切需要多种新的治疗和诊断靶点。为了加速实现到2025年开发出有效治疗阿尔茨海默病的国家目标，NIA创建了几个旨在确定新的阿尔茨海默病药物靶点的倡议，包括阿尔茨海默病加速药物伙伴关系（AMP-AD）。虽然很有希望，但我们对大多数新兴治疗假设和指定靶点的理解还不足以支持它们整合到药物发现计划中。我们认识到，支持将靶点整合到药物发现管道中所需的证据数量将远远超过任何一个团队的专业知识和能力，在此我们介绍阿尔茨海默病开放药物发现中心（Open- ad）。过去十年的活动已经明确表明，开放科学方法可以用于降低新治疗模式的风险，例如从AMP-AD中出现的模式，以催化药物靶点的生物学验证并启动新的商业药物发现计划。为了重振阿尔茨海默病药物发现管道，通过来自整个研究界的证据支持的多种支持良好的下一代阿尔茨海默病靶点组合，Open-AD将开发和公开传播资源（实验工具、试剂、探针、知识、数据），这些资源可以支持各种独立评估的靶点验证和药物发现。在目标1中，我们将制定一套优先的社区提名的治疗假设和靶点。在目标2中，我们将开发靶标启用包，其中包括用于靶标验证和药物发现的高质量，经过良好验证的试剂。在目标3中，我们将开发化学和生物探针。在Aim 4中，我们将快速和公开地分发所有Open-AD资产（包括探针），以便任何感兴趣的学术和/或商业研究者能够对候选药物靶点进行表征和实验验证。

There is an urgent need for a diverse portfolio of new therapeutic and diagnostic targets for Alzheimer’s disease (AD). To hasten progress towards the national goal of developing an effective treatment for AD by 2025, the NIA has created several initiatives designed to identify new AD drug targets, including the Accelerating Medicine Partnership for AD (AMP-AD). Although promising, our understanding of most of the emerging therapeutic hypotheses and nominated targets is not yet sufficient to support their integration into drug discovery programs. Understanding that the amount of evidence required to support the integration of a target into a drug discovery pipeline would far surpass the expertise and capabilities of any one group, here we introduce the Open Drug Discovery Center for Alzheimer’s Disease (Open-AD). The past decade of activity has conclusively shown that the open science approach can be used to de-risk new therapeutic modalities, such as the ones emerging from AMP-AD, to catalyze biological validation of drug targets and to launch new commercial drug discovery programs. To reinvigorate the AD drug discovery pipeline with a diverse portfolio of well-supported next generation AD targets supported by evidence from across the research community, Open-AD will develop and openly disseminate resources (experimental tools, reagents, probes, knowledge, data) that can support target validation and drug discovery across a wide variety of independent evaluations. In Aim 1, we will develop a prioritized set of community-nominated therapeutic hypotheses and targets. In Aim 2, we will develop target enabling packages that include high-quality, well-validated reagents for use in target validation and drug discovery. In Aim 3, we will develop chemical and biological probes. In Aim 4, we will rapidly and openly distribute all Open-AD assets – including probes – to enable characterization and experimental validation of candidate drug targets by any interested academic and/or commercial investigator.