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This funding opportunity announcement (FOA) encourages early-stage development of novel small molecule or biologic therapeutics for NINDS mission-relevant? Alzheimer's and related dementias: frontotemporal degeneration (FTD, including Picks disease and progressive supranuclear palsy), Lewy body dementias (LBD; including dementia with Lewy bodies (DLB) and Parkinsons disease dementia (PDD), vascular contributions to cognitive impairment and dementia (VCID), and multiple etiology dementias (MED). This FOA covers four stages of early therapy discovery/development with each stage gated by go/no-go milestones. Applicants may enter the program at the stage appropriate to their research. The R61 phase supports preparatory research stages 1 -3: 1) development of in vitro and/or ex vivo assays that can support therapeutic screening efforts, 2) screening efforts to identify and characterize potential therapeutic agents, and 3) therapeutic optimization, pharmacodynamic and pharmacokinetic studies. The R33 phase supports stage 4, in vivo efficacy studies in an animal model of disease. This FOA supports research to enable competitive follow-on applications that meet the entry criteria for the Blueprint Neurotherapeutics Network, Blueprint Biologics, or other similar later-stage translational programs.

This concept would support the development of pain clinical trainees as a means of enhancing the clinical pain workforce. It would fund 4 clinical pain T90/R90s that would provide robust post-doctoral fellowship research training in areas of clinical pain management that would benefit from further research. The T90/R90 mechanism is a NRSA program that supports comprehensive interdisciplinary research training programs at the undergraduate, predoctoral, and/or post-doctoral levels by capitalizing on the infrastructure of existing multidisciplinary and interdisciplinary research programs. The HEAL T90/R90 program would focus on training post-doctoral fellows with T90 trainees being those who are NRSA eligible and R90 trainees (maximum of 1 per award per year) being those who do not meet qualifications for NRSA support (including non-US citizens or residents). Trainees would either need to have a clinical degree or have a non-clinical degree but are interested in conducting clinical pain research. The T90/R90 training programs would provide mentoring and training to promote the successful transition of the trainees to independent research careers in academic or government settings. Unlike the T32 mechanism, the T90/R90 mechanism would support the dedication of 10% of the programs mentors time to mentoring the next generation of clinical pain researchers. The newly funded T90/R90s would work in coordination with the HEAL R24 Coordinating Center to ensure that trainees participate in the network, collaborative events/webinars, build relationships with basic and clinical science trainees, and attend the annual workshop. The NIH will prioritize funding T90/R90s universities and institutions that do not currently have a pain T32 or have not previously received funding for a pain T32. T90/R90 applicants are encouraged to partner with another university or institution to help increase the interdisciplinary nature of the mentors and trainees.

The purpose of the NINDS Postdoctoral Mentored Career Development Award is to support the ability of outstanding, mentored postdoctoral researchers to develop a potentially impactful research project with a comprehensive career development plan that will enable them to launch an independent research program. Candidates are encouraged to apply for support from this NINDS K01 any time between the second through fourth year of cumulative mentored postdoctoral research experience, and may be supported by this NINDS K01 within the first 6 years of cumulative postdoctoral research experience. Because the completion of a strong, well-planned, thorough career development plan, in addition to development of an impactful research project, is a critical aspect of this K01, applications are strongly encouraged early in the postdoctoral eligibility window. By the end of the proposed K01 award period, the candidate should be poised to begin an independent research career with a well-developed, impactful research project and the expertise required to become a leader in the field.This Funding Opportunity Announcement (FOA) is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary study to an existing trial, as part of their research and career development.

The purpose of the NINDS Postdoctoral Mentored Career Development Award is to support the ability of outstanding, mentored postdoctoral researchers to develop a potentially impactful research project with a comprehensive career development plan that will enable them to launch an independent research program. Candidates are encouraged to apply for support from this NINDS K01 any time between the second through fourth year of cumulative mentored postdoctoral research experience, and may be supported by this NINDS K01 within the first 6 years of cumulative postdoctoral research experience. Because the completion of a strong, well-planned, thorough career development plan, in addition to development of an impactful research project, is a critical aspect of this K01, applications are strongly encouraged early in the postdoctoral eligibility window. By the end of the proposed K01 award period, the candidate should be poised to begin an independent research career with a well-developed, impactful research project and the expertise required to become a leader in the field.This Funding Opportunity Announcement (FOA) is designed specifically for applicants proposing research that does not involve leading an independent clinical trial, a clinical trial feasibility study, or an ancillary study to a clinical trial. Applicants to this FOA are permitted to propose research experience in a clinical trial led by a mentor or co-mentor.

This is a reissue of RFA-MH-21-175 to comply with DMSP policy. The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application. The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged. Tools that can be used in a number of species/model organisms rather than those restricted to a single species are highly desired. Applications that provide approaches that break through existing technical barriers to substantially improve current capabilities are highly encouraged.

Reissue of RFA-MH-22-115 to comply with DMSP policy. The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis and manipulation of complex circuits and provide insights into cellular interactions that underlie brain function. Critical advances in the treatment of brain disorders in human populations are hindered by our lack of ability to monitor and manipulate circuitry in safe, minimally-invasive ways. Clinical intervention with novel cell and circuit specific tools will require extensive focused research designed to remove barriers to delivery of gene therapies. In addition to identification and removal of barriers, the need to specifically target dysfunctional circuitry poses additional challenges. Neuroscience has experienced an impressive influx of exciting new research tools in the past decade, especially since the launch of the BRAIN Initiative. However, the majority of these cutting edge tools have been developed for use in model organisms, primarily rodents, fish and flies. These cutting edge tools, such as viral delivery of genetic constructs, are increasingly adaptable to large brains and more importantly are emerging as potential human therapeutic strategies for brain disorders. A pressing need to develop tools for use in large brains, more directly relevant to the human brain is the focus of this initiative. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application.

The participating Institutes and Centers (ICs) are inviting applications to expand existing awards that are not currently focused on Alzheimers disease (AD) and its related dementias (ADRD) (e.g., frontotemporal dementia, Lewy body dementia, Vascular Contributions to Cognitive Impairment and Dementia (VCID), and multiple etiology dementias) to allow the research to develop such a focus.

This funding opportunity announcement (FOA) supports the development of PET radioligands that identify proteinopathies or pathological processes associated with the human biology of Alzheimer's disease related dementias (ADRDs). Activities supported under this FOA include, but are not limited to the in vitro screening of existing ligands against human ADRD brain tissue, medicinal chemistry support for development of new compounds and improvement of existing ligand specificity and selectivity, initial screening of ligands in appropriate animal models, and radioligand formulation and first-in-human testing. The Center without Walls should encompass research that will move promising ligands through in vitro and in vivo optimization to first-in-human studies. Applications must include an administrative core, a medicinal chemistry core, a clinical core, a scientific governance structure, and a minimum of two research projects with milestone plans that address workflows for screening of existing and newly derived ligands against human ADRD tissue and appropriate animal models. Synergy must be evident among Center research projects and cores, such that successful completion of the aims could not be accomplished without the Center structure. This FOA is in response to the Alzheimer's Disease Related Dementias (ADRD) challenges outlined in the 2016 update to the National Plan to Address Alzheimer's Disease.

This Notice of Funding Opportunity (NOFO) aims to support the establishment of programs to enhance research rigor and transparency practices within academic and research institutions to promote a culture of high-quality neuroscience research. Attention to principles of rigorous study design and transparent reporting are essential to enable the neuroscientific community, as well as the biomedical community at large, to design and perform valid experiments and to assess the value of scientific findings. Awards are intended to support the implementation of innovative programs, strategies, and approaches at the departmental, inter-departmental, or equivalent intra-institutional entity level.

More than 25 million Americans suffer from daily chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an overreliance in the prescription of opioids for chronic pain despite their poor ability to improve function and high addiction liability. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative pain treatment options are thus critically needed. Through targeted research efforts, the NIH HEAL Initiative aims to support the development of safe and effective devices to treat pain with little or no addiction liability. This funding opportunity announcement (FOA) is designed to support interdisciplinary research teams of multiple PD/PIs to investigate the mechanism of action of pain relief by medical devices with the overall goal of optimizing therapeutic outcomes for FDA-approved or -cleared technologies. Program teams are expected to accomplish goals that require considerable synergy and collaborative interactions. Teams must leverage appropriate multi-disciplinary expertise to develop new principles and methods for experimentation, analysis, and interpretation. Teams are encouraged to consider objectives that will produce major advances in the field of pain relief by medical devices.