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Drug Discovery for Nervous System Disorders
When beginning your next investigator-initiated application, consider the following NIH highlighted topic. The area of science described below is of interest to the listed NIH Institutes, Centers, and Offices (ICOs). This is not a notice of funding opportunity (NOFO).
Apply through an appropriate NIH Parent Funding Announcement or another broad NIH opportunity available on Grants.gov. Learn how to interpret and use Highlighted Topics.
Topic Description
Post Date: January 28, 2026
Expiration Date: January 28, 2027
Background
Nervous system disorders represent some of the most challenging therapeutic areas for successful drug approvals. The escalating global burden of death and disability for such diseases represents a significant worldwide public health challenge, and the rate of failure of new therapies for chronic progressive disorders of the nervous system is higher relative to other non-neurological conditions. Therefore, there is an urgent need to advance new and innovative therapeutic approaches and drug discovery tools for the treatment and prevention of nervous system disorders.
Purpose
The overarching purpose of this Highlighted Topic (HT) is to accelerate the process of drug discovery to enable the development of novel and effective treatments for nervous system disorders. More specifically this HT encourages applications aimed at discovery of therapeutic agents that affect fundamental processes associated with nervous system diseases, such as neuronal dysfunction, abnormalities in cell growth, migration, plasticity, connectivity, and cell death, by targeting molecules and cellular mechanisms such as neurotransmitters, bioactive lipids, neuromodulators, and neurotrophins; receptors and ion channels; second and third messenger systems; protein synthesis, aggregation, and degradation; brain energy utilization; gene expression; neural-glial communication; and oxidative, immunological, and inflammatory mechanisms.
Research projects may include activities to identify, optimize, and validate potential therapeutic candidates and may propose studies focused on all stages of the early drug discovery pipeline, from screening to candidate selection. Examples include the following:
- High, medium, or low-throughput assays, as well as counter-screening to assess the activity and selectivity of hit and lead compounds.
- Virtual screening and computational hit expansion following high-throughput screening (HTS) campaigns.
- Isolation, identification, characterization and synthesis of promising naturally occurring products.
- Medicinal chemistry to improve activity and selectivity of validated hit compounds against the target of interest.
- Later stage lead optimization to improve efficacy and pharmacokinetics.
- Application of machine learning (ML) at any step of the drug discovery stage, spanning from hit/lead identification to lead optimization
- Development of ligands to serve as research tools in support of proof-of-principle preclinical studies and the validation of novel therapeutic targets.
- Initial DMPK and toxicity studies of candidate therapeutics. This may include in vitro and/or in vivo testing.
- Evaluation of efficacy in cell-based or in vivo model systems that recapitulate critical molecular, cellular, or circuit/systems-level features of a specific nervous system disorder
- Development of novel delivery systems to target therapeutics to the brain.
Participating ICOs
NIA is interested in the discovery of novel therapeutics including small molecules and biologics aimed at delaying the onset or slowing the progression of: Alzheimer's Disease (AD), mild cognitive impairment (MCI), and other dementias of aging and age-related cognitive decline.
In the context of this announcement, NIA is not interested in projects aimed at repurposing therapeutics, developing combination therapies, or late-stage drug development activities such as:
- IND-enabling studies (e.g. toxicology and safety pharmacology)
- Chemistry, Manufacturing, and Control (CMC) activities
- Good Manufacturing Practices (GMP) synthesis
NIA believes this research would be most appropriately supported through research projects (e.g., R01, R21).
ICO Scientific Contact:Lorenzo M. Refolo, Ph.D.
[email protected]
The National Eye Institute (NEI) is interested in discovery of novel therapeutics including small molecules and biologics to treat diseases and disorders of the visual system, especially blinding eye diseases such as cataracts, glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, ocular pain and other conditions. The NEI is also interested in other visual system disorders such as strabismus and amblyopia that could be treated with pharmacological interventions. Each project should have a well-defined endpoint, achievable within the project time frame, for developing therapeutic candidates for a specific disease or disorder of the visual system. The steps towards this goal should be clearly delineated in a series of milestones that support the development of a novel therapeutic that can be eventually tested in a clinical trial. Investigators are encouraged to contact NEI program staff to discuss potential research projects.
ICO Scientific Contact:Paekgyu Lee, Ph.D.
[email protected]
NIDA is interested in the discovery of novel therapeutics including small molecules and biologics to treat substance use disorders (SUDs) or the adverse effects of addictive substances (e.g., overdose, withdrawal). The focus of the research projects could encompass screening, discovery, and optimization of novel small molecules or biologics and their evaluation for efficacy. The application of artificial intelligence (AI) and machine learning (ML) and other innovative methods to accelerate the discovery and optimization of novel lead molecules is encouraged. Of special interest to NIDA are projects focusing on the identification and pursuit of agents to modulate previously unrecognized or understudied targets for the treatment of mono- and polysubstance use disorders, as well as SUDs in the context of comorbidities, including HIV. Projects involving late-stage drug development activities such as IND-enabling studies are considered out of scope for this specific announcement.
ICO Scientific Contact:Subramaniam Ananthan, Ph.D.
[email protected]
The National Institute of Mental Health (NIMH) has an interest in applications proposing the discovery and development of novel small molecules and biologics to pursue innovative targets for the treatment of mental disorders, including schizophrenia, autism spectrum disorder, treatment-resistant depression, bipolar disorder, post-traumatic stress disorder, HIV-induced CNS dysfunction, and neurodevelopmental disorders that are aligned with NIMH genetics priorities.
NIMH has published guidelines and priorities for applicants considering animal neurobehavioral approaches in research relevant to mental illnesses, summarized in NOT-MH-19-053. Applicants are strongly encouraged to contact NIMH program staff to discuss potential research projects before application submission to determine the alignment of the planned studies with the priorities of the institute.
Yael Mandelblat-Cerf, Ph.D.
[email protected]
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