AD Related Dementias – Specific
Develop better FTLD in vivo and cell-based model systems.
- Generate validated and standardized in vivo animal and cell-based models of TDP-43, FUS, GRN haploinsufficiency, and C9orf72 expansion disease, which recapitulate key biochemical, anatomical, neuropathological and functional aspects of FTD.
- Develop and validate in vivo functional assays and neuropathological endpoints for mammalian models that are aligned with the anatomical sites affected in FTD.
Summary of Key Accomplishments
In addition to supporting the development of better FTD disease models through our standard grant mechanisms such as NS097273 which uncovered a potential mechanism contributing to neurodegeneration by the FTD-linked mutation in the C9ORF72 gene, the NIH also released a targeted call for applications in this area in 2019 (PAR-19-167).
Examples of funded awards from this program include the characterization of a non-human primate model found to have a spontaneous mutation identical to that found in people with FTD , the development of mouse models that more completely mimic human disease at the genetic level, and the development of "organs-on-a-chip" that put cells grown in the lab in more biologically-relevant conditions with the potential for informing future clinical trials. Future work is progressing to develop models that better inform on specific disease mechanisms, biomarker discovery, and therapeutic target identification in FTD, while model generation is also being expanded to include computational (i.e., big data) models.
This information is current as of July 2022.
- Research Implementation Area
- AD Related Dementias - Specific
- In Progress
- RFA-NS-19-027: Human Three-Dimensional Cell Model Systems for Alzheimer's Disease-Related Dementias (ADRDs) (UG3/UH3 Clinical Trial Not Allowed)
- PAR-19-167: Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33 Clinical Trial Not Allowed)
- RFA-TR-19-014: "Clinical Trials" on a Chip: Tissue Chips to Inform Clinical Trial Design and Implementation in Precision Medicine (UG3/UH3 - Clinical Trial Not Allowed
Research Programs and Resources
- Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33)
- Human Three-Dimensional Cell Model Systems for Alzheimer's Disease-Related Dementias (ADRDs) (UG3/UH3)
- A microphysiologic multicellular organ-on-chip to inform clinical trials in FTD/ALS
- NINDS Human Cell and Data Repository (NHCDR)