NINDS funding opportunities for Alzheimer’s Disease‐Related Dementia therapy development

AbstractBackgroundGoal 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.MethodAll 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.ResultMulti‐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.ConclusionThrough these initiatives, NINDS hopes to provide a comprehensive pipeline for ADRD therapy development from target validation to the clinic.