Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Development and Validation of Model Systems to Facilitate Neurotherapeutic Discovery (R61/R33 Clinical Trial Not Allowed)
Funding Agency:
- National Institutes of Health
The NOFO will support applications to develop animal models with their matched controls (when not already available) for neurological or neuromuscular disease that recapitulate aspects of the disease pathophysiology as well as its etiology, where endpoints or markers of disease are similar and measurable in the animal model and human disease (i.e., neurological deficits, patterns of activation using functional Magnetic Resonance Imaging (fMRI) or electroencephalography (EEG), measurable genetic markers, functional or behavioral read-out, disease progression, etc.). In addition, it will support the development and validation of ex vivo testing systems with their matched controls that utilize existing human or animal cell systems (i.e., induced Pluripotent Stem Cells (IPSC)). Applications for use or development of iPSCs should review NOT-NS-24-019. In addition, this NOFO can support development and validation of new endpoints or readouts that better reflect the human condition.
Since this NOFO does not support the development of animal models or model systems for the purpose of testing hypotheses about disease etiology, it is assumed that model development will be based upon widely accepted hypotheses or knowledge regarding disease etiology. Projects looking to gain basic understanding of human disease etiology should instead consider a basic science NOFO.
The knowledge gained from these studies should lead to the development of "next generation" translational models of neurological disease. The models developed and validated as a result of applications to this NOFO should provide an improved “translational toolkit” that will better predict the efficacy and safety of new therapeutic entities, thereby facilitating future drug discovery and development in the field of neurological disorders and stroke.
Applications that propose to validate existing models are also appropriate for this NOFO. However, development of de novo models without validation is not appropriate.
Phased Award Milestones
Transition from the R61 to the R33 phase is contingent upon the successful completion of proposed milestones. Milestones are metrics that are quantifiable for measuring success that can be used for go/no-go decision-making at the R61/R33 transition point and should have timelines and quantitative criteria associated with them. NINDS emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress (see https://www.ninds.nih.gov/funding/preparing-your-application/preparing-r...). Specific Aims or a list of activities planned for each year are not considered milestones because they do not provide decision-making goals. For milestone examples, please see https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/Funding-Programs-Researchers/IGNITE.
Examples of activities in the R61 Phase include, but are not limited to:
- Initial development of the model or ex vivo system and matched control
- Any optimization of the above related to feasibility, endpoint range, reproducibility and sensitivity, potential to scale up for validation studies (breeding, aging, etc.), specificity of the model system as it relates to the disease or endpoint measures, identification of confounding variables, etc.
- Complete internal validation for endpoints used in the model compared to matched control
Examples of activities in the R33 Phase include, but are not limited to:
- All external validation studies, including comparisons of phenotype to what is known about human disease, comparisons of model disease etiology to what is known about the human disease and efficacy of clinically validated therapeutic agents (if available) in the new model system compared to matched control
- Independent replication at another site
Collaborations
Demonstration of collaborative relationships between applicants with preclinical and clinical drug development expertise (such as biostatisticians and clinicians) is highly encouraged. Collaborations with a clinician who has an understanding of the human condition can aid in developing models with clinical relevance. It is preferred that the collaborating clinician is listed as a co-investigator or a formal member of the investigative team. Alternatively, a letter of support from the collaborating clinician can be used to demonstrate involvement in the project but should include a plan for collaboration with the principal investigator. The clinician should have demonstrated experience in the development of therapeutic entities to treat neurological disease.
Additional Considerations:
- Applicants are strongly encouraged to contact NINDS Scientific/Research staff to discuss potential research projects prior to submitting an application.
- Small Business applicants who are eligible for the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are strongly encouraged to submit through either the SBIR or STTR Omnibus Solicitations (https://sbir.nih.gov/funding#omni-sbir) or other appropriate SBIR or STTR funding opportunities to take advantage of the congressionally mandated set-aside specifically for small businesses. Please see https://www.ninds.nih.gov/Funding/Small-Business-Grants for more information about the programs.
- Prior to funding an application, NINDS Program staff may contact the applicant to discuss the proposed milestones and any changes suggested by the NINDS review panel or Program staff. A final set of approved milestones will be specified in the Notice of Award.
Applications Not Responsive to this NOFO:
Non-responsive studies include those that involve any of the following activities:
- Applications containing the following therapeutic discovery/development activities:
- Test agent screening/identification (for support for this work, please consider PAR-25-059)
- Studies aimed at evaluating a potential therapeutic agent for efficacy or safety (for support for this work, please consider PAR-25-058)
- Applications containing the following basic science activities:
- Studies of disease mechanism in the newly developed model
- Studies of disease mechanism in humans or human samples; face and construct validations of the newly developed model should be based on widely accepted hypotheses or knowledge regarding human disease etiology. (Projects looking to gain basic understanding of human disease etiology should instead consider a basic science NOFO.)
- Development of animal and ex vivo cellular models for the purpose of understanding disease etiology
- Identification of drug targets
- Discovery and development of diagnostic, monitoring, predictive or prognostic biomarkers (for support for this wok, please consider the NINDS Biomarker Program)
- Applications with a significant focus (e.g. an entire aim) on developing pharmacodynamic biomarkers
- Development of devices (for support for this work, please consider the NINDS Translational Devices Program) device/drug combinations, surgical procedures, diagnostics, and rehabilitation strategies
Direct Costs cannot exceed $499,000 in any one year and cumulative direct costs for the three year project cannot exceed $750,000.
February 18, 2025; June 18, 2025
Becky Roof, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Email: rebecca.roof@nih.gov