背景:解决阿尔茨海默病(AD)的国家计划的目标1是到2025年预防和有效治疗AD和AD相关痴呆(ADRD)。为了这个目标,NINDS计划在2024年提供14个ADRD资助机会,以支持培训,基本机制,翻译,和ADRD的临床研究。这里,我们描述了ADRD转化疗法开发计划,其中包括1)多目标验证,2)早期治疗发展,3)基因组编辑和4)动物模型的开发和验证。Note,不需要ADRD特定的资金机会。ADRD研究人员还可以利用NINDS现有的计划,例如用于小分子或生物治疗开发的NIH神经治疗学蓝图(BPN)。这些程序支持优化,制造,IND支持研究,并通过结合赠款和补充获得NIH提供的CRO和顾问,首次在人体临床试验中。
方法:这里讨论的所有概念都得到了批准,然而,NIH不能保证未来的资助机会,奖励机制,或资金分配。资助机会只有在NIH指南中发布时才是官方的。
结果:ADRD概念的多目标验证旨在支持研究,以验证未来治疗开发的多个目标,从而更好地反映疾病的复杂性。早期治疗开发概念将支持小分子或生物疗法的开发,并将重新发行RFA-NS-22-059,支持测定开发。治疗性筛查,优化,和体内功效工作,为后期计划做准备。ADRD概念的基因组编辑将支持专注于体细胞基因编辑的早期翻译研究,期望研究将解决基因编辑方法的可行性,并将重新发行RFA-NS-23-017。PAR-23-154“阿尔茨海默病相关痴呆(ADRD)模型的开发和验证”支持ADRD的临床和病理生理相关模型的开发和验证,可用于未来的治疗开发。模型应反映人类状况的多个方面,包括内部,脸,construct,并尽可能进行预测性验证。
结论:通过这些举措,NINDS希望为从目标验证到临床的ADRD治疗开发提供全面的管道。
BACKGROUND: Goal 1 of the National Plan to Address Alzheimer\'s Disease (AD) is to prevent and effectively treat AD and AD-related dementias (ADRD) by 2025. Toward this goal, NINDS plans 14 ADRD funding opportunities for 2024 to support training, basic mechanisms, translational, and clinical research for ADRD. Here, we describe ADRD translational therapy development initiatives, which include 1) multi-target validation, 2) early-stage therapy development, 3) genome editing and 4) animal model development and validation. Note, ADRD specific funding opportunities are not required. ADRD researchers can also take advantage of NINDS existing programs such as the NIH Blueprint for Neurotherapeutics (BPN) for Small Molecule or Biologic therapy development. These programs support optimization, manufacture, IND-enabling studies and first in human clinical trials through a combination of grants and complementary access to NIH-provided CROs and consultants.
METHODS: All concepts discussed here are approved, however NIH cannot guarantee future funding opportunities, award mechanisms, or funding allocation. A funding opportunity is only official when published in the NIH Guide.
RESULTS: Multi-Target Validation for ADRD concept has the goal to support research that would validate multiple targets for future therapy development that better reflect the complexity of disease. Early-Stage Therapy Development concept would support the development of small molecule or biologic therapeutics and would be a reissue of RFA-NS-22-059, which supported assay development, therapeutic screening, optimization, and in vivo efficacy work in preparation for later-stage programs. Genome Editing for ADRD concept would support early translational research focused on somatic cell gene editing with the expectation that studies will address feasibility of the gene editing approach and would be a reissue of RFA-NS-23-017. PAR-23-154 \"Development and Validation of Models for Alzheimer\'s Disease-Related Dementias (ADRD)\" supports the development and validation of clinically- and pathophysiologically-relevant models of ADRD that can be used for future therapy development. Models should reflect multiple aspects of the human condition and include internal, face, construct, and predictive validation to the extent possible.
CONCLUSIONS: Through these initiatives, NINDS hopes to provide a comprehensive pipeline for ADRD therapy development from target validation to the clinic.