Optimization of Genome Editing Therapeutics for Alzheimer's Disease-Related Dementias (ADRD) (U01 - Clinical Trials Not Allowed)

Background
This Notice of Funding Opportunity (NOFO) is issued by the National Institutes of Health (NIH), specifically the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA). The goal is to support the optimization of promising genome editing-based therapeutic leads for Alzheimer's Disease-Related Dementias (ADRD) towards IND-enabling studies.

This initiative aligns with Goal 1 of the National Plan to Address Alzheimer's Disease, which aims to prevent and effectively treat Alzheimer's disease and ADRD by 2025. The NOFO encourages applications that translate genome editing technologies into treatments for various ADRD disorders, including Frontotemporal dementia (FTD), Lewy body dementias (LBD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), and Multiple Etiology Dementias (MED).

Grant Details
The NOFO supports the characterization and optimization of therapeutic leads that demonstrate potential as genome editing therapeutics. Successful projects will deliver an optimized candidate with demonstrated bioactivity, manufacturability, biodistribution, in vivo efficacy, target engagement, and optimal dosing.

Key tasks include:
- Identification and optimization of genome editing therapeutic leads using ADRD-related in vitro or animal models.
- Optimization of delivery systems and Chemistry, Manufacturing, and Control (CMC) activities for future IND-enabling studies.
- Development of a regulatory strategy for early-stage interactions with regulatory agencies.
- Activities may include improving gene editing efficiency, specificity, bioavailability, conducting proof-of-concept studies in vitro and in vivo, optimizing production processes, and validating target engagement assays.

Eligibility Requirements
Eligible applicants include higher education institutions, nonprofits, for-profit organizations (including small businesses), local governments, state governments, tribal governments, federal agencies, U.S. territories or possessions, independent school districts, public housing authorities/Indian housing authorities, faith-based organizations, community-based organizations, regional organizations. Non-domestic entities are not eligible to apply.

Period of Performance
The maximum project period is five years. The earliest start date for funded projects is November 19, 2024.

Grant Value
NIH intends to commit a total budget of up to $3 million per year to fund up to 2 awards. Application budgets are limited to no more than $1 million in direct costs per year.