Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD and other ADRDs (R01 - Clinical Trial Not Allowed)

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Description

This NIH funding opportunity supports research aimed at deepening mechanistic understanding of TDP-43 proteinopathies, which are implicated in several neurodegenerative diseases including Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), Frontotemporal dementia (FTD), and other Alzheimer’s Disease-Related Dementias (ADRDs). The goal is to elucidate causal cellular and molecular relationships between TDP-43 pathology and clinical phenotypes, as well as to identify distinct and overlapping mechanisms among different TDP-43 proteinopathies.

Research should include comparative studies between at least two TDP-43 proteinopathies, with one being an ADRD, such as LATE (with or without Alzheimer’s disease neuropathological change) or Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). Studies may explore interactions with other pathologies (e.g., TMEM106B, tau, alpha-synuclein, vascular pathology) and employ various model systems including animal models, cellular systems, organoids, and postmortem tissues.

The initiative aligns with the National Plan to Address Alzheimer’s Disease, aiming to prevent and treat AD and ADRDs by 2025. It responds to research priorities from the 2022 NINDS ADRD Summit, emphasizing the need to understand overlapping pathologic mechanisms and improve diagnosis and awareness.

Applications must focus on mechanistic investigations and are not intended for descriptive, correlative, epidemiological, or biomarker discovery studies. Clinical trials are explicitly not allowed.

Due Dates

• New Applications: October 4, 2023, by 5:00 PM local time of applicant organization
• Expiration Date: October 5, 2023
• Note: This FOA has been reissued as PAR-24-148 for future submissions.

Funding Amount

• Direct Costs: Up to $500,000 per year
• Project Period: Up to 5 years
• Total Budget: NINDS intends to commit up to $3,750,000 per year to fund up to five awards, contingent on appropriations and meritorious applications.

Eligibility

• Eligible Applicants:
  • Public and private institutions of higher education (including HBCUs, Hispanic-serving institutions, tribal colleges, etc.)
  • Nonprofits with or without 501(c)(3) status (excluding institutions of higher education)
  • For-profit organizations including small businesses
  • State, county, city, township, and special district governments
  • Federally recognized and other Native American tribal governments and organizations
  • Independent school districts, public housing authorities, faith-based and community-based organizations, regional organizations
• Foreign Institutions: Not eligible to apply; however, foreign components of U.S. organizations are allowed.
• Clinical Trials: Not allowed under this FOA.
• Cost Sharing: Not required.

Application Process

• Applications must be submitted electronically via Grants.gov and tracked in eRA Commons.
• Applicants must follow the SF424 (R&R) Application Guide and use FORMS-H application packages.
• The Research Strategy must address how the project will advance mechanistic insights into TDP-43 pathology and its clinical outcomes, including rigorous experimental design and transparency.
• A Data Management and Sharing Plan is required for all applications generating scientific data.
• Limited appendix materials are allowed (e.g., blank questionnaires).
• Applications must include at least one human subjects study record or delayed onset study record if human subjects are involved.
• Early consultation with NINDS scientific staff is encouraged.

Review Criteria

Applications will be evaluated on:

• Significance: Importance of the problem, rigor of prior research, potential to advance knowledge of TDP-43 mechanisms and clinical outcomes.
• Investigator(s): Qualifications, expertise, and collaborative approach of the research team.
• Innovation: Novelty of concepts, approaches, or methodologies.
• Approach: Soundness of strategy, methodology, plans to address prior research weaknesses, consideration of biological variables, and feasibility.
• Environment: Institutional support, resources, and collaborative arrangements.
• Additional Considerations: Protection of human subjects, inclusion of diverse populations, use of vertebrate animals, biohazards, resource sharing, and budget justification.

Additional Information

• Applications not comparing at least two TDP-43 proteinopathies (one being an ADRD), or lacking mechanistic investigations, will be administratively withdrawn.
• Mechanisms and risk factors across diverse populations should be considered to promote health equity.
• The award is subject to NIH Grants Policy Statement terms and conditions.
• Recipients must comply with federal civil rights laws and policies on data sharing, human subjects protection, and animal welfare.

External Links

• Funding Opportunity Announcement (PAR-23-212)
• NIH Grants Policy Statement
• NIH Data Management and Sharing Policy
• National Plan to Address Alzheimer’s Disease
• NINDS ADRD Summit 2022
• NIH Research Involving Human Subjects
• NIH Grants & Funding Glossary

Contact Information