Funding Opportunity Number: RFA-NS-24-032
Due Dates
Letter of Intent: May 20, 2024
Submission: September 20, 2024
Letter of Intent: June 20, 2024
Submission: October 21, 2024
Purpose/Research Objectives
Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer’s disease (AD) and Alzheimer’s Disease Related Dementias (ADRD). ADRD are defined as Frontotemporal dementia (FTD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy Body Dementias (LBD) and Multiple Etiology Dementias (MED). Starting in 2012, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held research summits to assess the needs and set AD/ADRD research implementation milestones. The NINDS ADRD Summit in 2022 resulted in ADRD research priorities for advancing the state-of-the-science toward meeting Goal 1 of the National Plan. This NOFO is responsive to several high priority milestones established at the 2022 ADRD Summit (https://www.ninds.nih.gov/news-events/events/adrd-summit-2022, including establishing experimental models to identify disease-relevant mechanisms and developing new experimental models that incorporate aging with pathologic and molecular phenotype to advance understanding of pathophysiology and to support drug discovery.
There is a need to generate more human cellular models that reflect multiple aspects of these complex ADRD disorders. Desirable models can cover various disease stages, multiple brain cell types, vascular elements, multiple interacting pathologies, and incorporate relevant genetic, pathologic and molecular phenotypes. Complex cellular models that can advance key molecular pathways in a pathophysiologically relevant context and that are validated against human data are particularly needed because they are valuable for modeling molecular disease mechanisms and networks, perturbations, and therapeutic targets and interventions. These model systems need to be highly reproducible and translatable and are strengthened by a multidisciplinary approach (e.g., bioengineering, microfluidics, disease biology, pathology, electrophysiology, biostatistics, clinical science, etc.). Many factors are critical to validate cell models against human ADRD data, such as differentiation, maturation, and age-appropriate molecular and physiological signatures of brain cell types, how well the model mimics in vivo tissue structure and physiological conditions, cellular interactions and multicellular architecture that represents characteristics of brain pathology, functional representation and phenotypes of diseased human biology, how well characteristics are maintained over time, different mechanisms/genetics/risk factors in diverse human populations, etc.
This NOFO supports the development and validation of novel, complex, and pathophysiologically relevant human cellular models of ADRD. The cellular model system needs to reflect multiple aspects of the human condition as much as possible, such as capturing the multiple pathologies and brain cell types observed in ADRD. Validation is required, including face and construct validity. Human cellular models could be developed and validated with the goal of supporting therapeutic development or better understanding of human disease mechanisms and mechanisms that cause predisposition or resilience to developing ADRD.
For more information, please see the opportunity website.