Functional Target Validation for Alzheimer's Disease-Related Dementias

The National Institute of Neurological Disorders and Stroke (NINDS) is interested in supporting ambitious research projects that propose comprehensive functional validation of newly identified therapeutic target candidates for Alzheimer’s Disease–Related Dementias (ADRD). A major barrier to the development of effective treatments for ADRD, as well as other complex central nervous system disorders, is the lack of well-validated targets that are clearly linked to disease mechanisms. Successful translation of basic discoveries into the clinic depends on the rigor of target validation and confidence in a causal relationship between modulation of a target and its functional physiological consequences relevant to treating or preventing disease. This initiative aims to de-risk subsequent translational research and accelerate the development of novel therapeutic strategies. NINDS believes that this initiative would be most appropriately supported by a phased award mechanism (for example, R61/R33). In the initial phase, support would be provided for the development of customized technologies, models, and protocols to modulate the expression or activity of candidate targets and to assess their physiological consequences in relevant in vitro and in vivo disease models. Upon successful achievement of predefined, milestone-based technical feasibility and proof-of-concept criteria, projects would transition to the second phase focused on measuring and cross-validating the effects of target modulation across multiple experimental modalities and collaborating laboratories, in accordance with NIH rigor and reproducibility guidelines. Applications are not being solicited at this time. Notice is being provided to allow potential applicants sufficient time to develop responsive projects and establish appropriate cross-disciplinary collaborations.