Drug Discovery For Nervous System Disorders (R21 Clinical Trials Not Allowed)

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Description

This NIH Funding Opportunity Announcement (FOA) encourages exploratory and developmental research (R21 mechanism) aimed at discovering novel compounds and biologics for the prevention and treatment of nervous system disorders, particularly those related to mental illnesses, substance use disorders (SUD), alcohol use disorder (AUD), and aging. The FOA supports projects that focus on:

• Identification, design, synthesis, and preclinical testing of small molecules and biotechnology products (e.g., proteins, antibodies, peptides, gene-based therapies, cell therapies).
• Hit-to-lead chemistry to improve compound activity.
• Lead optimization to enhance efficacy and pharmacokinetics.
• Initial drug metabolism and pharmacokinetic (DMPK) and toxicity studies (excluding IND-enabling and clinical development studies).
• Development of novel delivery systems targeting the brain.
• Use of innovative assays, including in vitro, ex vivo, and in vivo models that reflect disease-relevant molecular, cellular, or circuit-level features.

The FOA emphasizes novel approaches, including the application of machine learning (ML) and computational methods for drug design, screening, and optimization. Projects should address unmet therapeutic needs and provide clear go/no-go criteria for advancing candidates.

Not supported are projects involving human subjects, clinical trials, IND-enabling studies, safety pharmacology, or Good Manufacturing Practices (GMP) synthesis.

Institute-Specific Interests

• NIMH: Focus on novel molecules targeting mental illnesses (e.g., schizophrenia, ASD, PTSD), including neuronal dysfunction and neuroinflammation related to HIV and antiretroviral therapy.
• NIDA: Novel therapeutics for substance use disorders and related adverse effects.
• NIAAA: Small molecules targeting alcohol misuse and AUD, including agents addressing protracted abstinence and co-morbid psychiatric conditions.
• NIA: Therapeutics aimed at modifying behavioral symptoms or slowing progression of Alzheimer's disease, mild cognitive impairment, and other dementias; repurposing or combination therapies are not of interest.

Due Dates

• New applications: October 16, 2024
• Renewal/Resubmission/Revision: November 16, 2024

Applications are due by 5:00 PM local time of the applicant organization. If the due date falls on a weekend or federal holiday, the deadline is extended to the next business day.

Funding Amount

• Direct costs up to $275,000 total over 2 years.
• No more than $200,000 in direct costs allowed in any single year.
• Project period: up to 2 years.

Eligibility

Eligible Applicants

• Higher Education Institutions (public/state controlled and private)
• Nonprofits (with or without 501(c)(3) status, excluding institutions of higher education)
• For-profit organizations (including small businesses)
• Local governments (state, county, city/township, special districts)
• Native American tribal governments and organizations (federally recognized and others)
• Federal agencies
• Independent school districts
• Public housing authorities
• Faith-based or community-based organizations
• Regional organizations
• Foreign institutions and components of U.S. organizations

Additional Eligibility Notes

• Multiple applications allowed if scientifically distinct.
• Resubmissions must comply with NIH policies on overlapping applications.
• Clinical trials are not allowed under this FOA.
• Applicants must complete all required registrations (DUNS/UEI, SAM, eRA Commons, Grants.gov) prior to submission.
• PD(s)/PI(s) must have an eRA Commons account.

Application Process

• Applications must be submitted electronically via Grants.gov and tracked in eRA Commons.
• Use SF424 (R&R) application forms, following FORMS-H instructions.
• Include a detailed Research Strategy addressing significance, innovation, and approach.
• Address the competitive landscape and justify novelty and unmet needs.
• Provide clear go/no-go criteria for candidate advancement.
• Include a Data Management and Sharing Plan as per NIH policy.
• Follow all NIH instructions for budget preparation, including justification for all costs.
• Limited appendix materials allowed (e.g., blank forms, consent forms).
• No human subjects or clinical trial components allowed.
• Contact NIH Scientific/Research contacts prior to submission for guidance.

Review Criteria

Applications will be evaluated on:

• Significance: Importance of the problem and potential impact on the field.
• Investigator(s): Qualifications and expertise of the research team.
• Innovation: Novelty of therapeutic targets, approaches, or methodologies.
• Approach: Soundness of strategy, methodology, and analyses; plans to address rigor and reproducibility.
• Environment: Institutional support and resources.

Additional considerations:

• Protection of human subjects (generally not applicable).
• Inclusion of women, minorities, and individuals across the lifespan (generally not applicable).
• Use of vertebrate animals, if applicable.
• Biohazards and safety.
• Resource sharing plans.
• Budget justification.

Award Administration

• Awards are subject to NIH Grants Policy Statement terms and conditions.
• Recipients must comply with federal civil rights laws and policies.
• Annual progress reports (RPPR) and financial reports are required.
• Reporting of subawards and executive compensation as per federal requirements.
• Compliance with NIH Data Management and Sharing Policy is required.

Contact Information

External Links

• Funding Opportunity Announcement (PAR-22-032)
• NIH Grants & Funding
• NIH SF424 (R&R) Application Guide - Forms Version H
• NIH Data Management and Sharing Policy
• NIH Grants Policy Statement
• NIH eRA Commons
• Grants.gov