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Functional Target Validation for Alzheimer's Disease-Related Dementias (R61/R33 Clinical Trial Not Allowed)

National Institutes of Health

This NOFO invites applications that propose the comprehensive functional validation of newly identified therapeutic target candidates for Alzheimer's Disease-Related Dementias (ADRD). This NOFO seeks to promote critical target validation approaches to help de-risk subsequent translational research and accelerate the advancement of novel therapies for ADRD. Target(s) or molecular pathway(s) to be considered for validation must have been already identified using tissue expression or genetic data generated in human samples. In its initial phase, this NOFO provides support for up to two years (R61 stage) for the development of customized technologies, models, and protocols to modulate the expression or activity of target candidate(s) in cells and/or tissues and monitor their functional biological consequences in vitro or in vivo disease models. Upon demonstration of technical feasibilities, a second phase (R33 stage) will carefully and reproducibly measure and cross-validate the impact of the target modulation in different modalities across collaborating laboratories using the NIH rigor and reproducibility guidelines. This NOFO will support applications that address objectives for both the R61 and R33 phases and are expected to have a substantial collaborative effort between independent laboratories.

This NOFO is not specific for anyone or group within the ADRD spectrum of disorders. Disorders covered in these applications are frontotemporal degeneration (FTD), Lewy body dementias (LBD) (including dementia with Lewy bodies (DLB)), Parkinson disease dementia (PDD), vascular contributions to cognitive impairment and dementia (VCID), and mixed dementias including the multiple etiology dementias (MED).

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