Translational and Therapeutics Core

项目总结 转化性治疗核心(TTC)将提供必要的基础设施和专业知识 加速阿尔茨海默病(AD)及AD相关新疗法的临床前开发 痴呆(ADRD)。TTC将填补AD/ADRD新疗法开发中的一个关键空白 通过促进翻译科学的两个关键组成部分，这些关键组成部分在 学术界：(1)基础科学发现的人类靶标验证，以及(2)网络医学方法 确定已经存在的用于药物再用途的药物。这方面的一个关键方面是人类数据指向目标 通过临床经验、人类遗传学和组织表达领域进行验证。这是特别的 由于缺乏高质量的组织和疾病的复杂性，AD/ADRD领域的后勤挑战。 通过建立克利夫兰阿尔茨海默病研究中心(CADRC)的核心，TTC 将与Biomarker Core(BC)密切合作，不仅提供深入表型的生物 样本，但专家对ADRD的异质性提供了指导。TTC将为CADRC带来丰富的 共享资源包括大学医院的哈灵顿发现研究所(HDI)，它是 哈灵顿发现与发展项目，这是一项旨在实现创造性的国际倡议 科学家们将把他们的发现推进到新药上，这种新药将通过提供 资金和药物开发支持，以弥合基础发现和临床领域之间的差距。 TTC由阿尔茨海默氏症药物发现基金会(ADDF)主任安德鲁·派珀博士领导- 哈灵顿学者计划，该计划支持科学家开发预防、治疗和治愈的药物 AD/ADRD。TTC将确定和支持研究人员开发目前针对 AD/ADRD通过Pieper博士与ADDF的关系，在CADRC的地方和国家和国际上 和HDI(特定目标1)。研究人员开发了对与以下相关的新假说的临床前支持 AD/ADRD将通过程博士的基于网络的方法来支持，以识别 可能被重新用于治疗AD/ADRD。TTC还将适用与具体目标1中相同的原则 支持研究人员在其他医学研究领域开发新的疗法或假说， 也适用于AD/ADRD，以支持开发新疗法的创新的关键多样性 对于AD/ADRD(具体目标2)。此外，与CADRC Biomarker Core(BC)的协调将使 TTC以促进识别与新的治疗方法相关的标记物，这可能会应用于 未来的临床试验或病人护理。通过提供用于在人体组织中使用的靶向验证的途径和资金 CADRC生物标记物和神经病理学核心中不断增长的生物样品收集，TTC将使 CADRC将有意义地推进患者新疗法的开发。

PROJECT SUMMARY The Translational Therapeutics Core (TTC) will provide the infrastructure and expertise necessary to accelerate preclinical development of novel therapeutics for Alzheimer’s disease (AD) and AD-related dementias (ADRD). The TTC will fill a critical void in the development of new therapeutics in the AD/ADRD field by facilitating 2 critical components of translational science that are desperately under supported in academia: (1) human target validation of basic science findings, and (2) network medicine approaches to identify already existing agents for drug repurposing. A critical aspect of this is human data towards target validation, through the realms of clinical experience, human genetics, and tissue expression. This is particularly logistically challenging in the field of AD/ADRD due to scarcity of quality tissue and disease complexity. Through the establishment of the Cleveland Alzheimer’s Disease Research Center (CADRC) Cores, the TTC will work closely with the Biomarker Core (BC) to provide not only access to deeply phenotyped biological samples, but expert guidance in the heterogeneity of ADRD. The TTC will bring to the CADRC a wealth of shared resources including the Harrington Discovery Institute (HDI) at University Hospitals, which is part of the Harrington Project for Discovery & Development, an international initiative designed to enable inventive scientists to advance their discoveries into novel medicines that will improve human health by providing funding and drug development support to bridge the gap between basic discovery and the clinical realm. The TTC is led by Dr. Andrew Pieper, Director of the Alzheimer’s Drug Discovery Foundation (ADDF) – Harrington Scholar Program, which supports scientists to develop drugs that will prevent, treat, and cure AD/ADRD. The TTC will identify and support researchers developing therapeutics currently targeted for AD/ADRD locally in the CADRC, and nationally and internationally through Dr. Pieper’s relationship with ADDF and HDI (Specific Aim 1). Researchers who have developed preclinical support for novel hypotheses related to AD/ADRD will be supported through Dr. Cheng’s methods for network-based approaches to identify drugs that might be repurposed for treating AD/ADRD. The TTC will also apply the same principles as in Specific Aim 1 to support researchers developing novel therapeutics or hypotheses in other areas of medical research that might also be applied to AD/ADRD, in order to support critical diversity of innovation for developing new treatments for AD/ADRD (Specific Aim 2). In addition, coordination with the CADRC Biomarker Core (BC) will enable the TTC to facilitate identification of markers related to new therapeutic approaches, which might be applied in future clinical trials or patient care. By providing access and funds for target validation in human tissue using the growing biospecimen collections in the CADRC Biomarker and Neuropathology Cores, the TTC will enable the CADRC to meaningfully advance development of new treatments for patients.