NIH – Drug Discovery For Nervous System Disorders (R01, R21)

R01 FOA
(PAR-16-041)

R21 FOA
(PAR-16-042)

National Institute of Mental Health
National Institute on Alcohol Abuse and Alcoholism
National Institute on Drug Abuse

Significant advances in neuroscience, genetics, and basic behavioral science, together with technological developments, have provided a rich knowledge base for identifying new molecular targets for drug discovery, and developing rational pharmacotherapies for the treatment of a wide variety of nervous system disorders. With the wealth of potential new drug targets, the opportunity exists to accelerate the process of drug discovery and development to make quantum leaps toward novel and effective treatments for mental disorders, drug and alcohol abuse, and nervous system disorders associated with aging.

Through this funding opportunity the National Institute of Mental Health (NIMH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA) encourage the submission of research grant applications that aim to translate this wealth of basic science findings into the conceptualization, discovery, and preclinical evaluation of innovative therapeutics for mental illnesses, drug and alcohol abuse, and nervous system disorders associated with aging, with the goal of accelerating the development of new treatments for these diseases.

The objective of this FOA is to stimulate research in the discovery, design, and preclinical testing of innovative and effective therapeutics aimed at prevention or treatment of nervous system disorders of primary interest to the NIMH, NIAAA, and NIDA. Projects focused on novel approaches and targets are highly encouraged. Projects designed for target identification or elucidation of disease mechanisms are not covered under this announcement.

Applications aimed at the discovery of novel agents for ameliorating, modifying, or correcting potential aberrations in brain signaling are encouraged. These agents should be designed to affect fundamental processes associated with disease, 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 any activities required 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 of these activities may include, but are not limited to:

• Preliminary identification of candidate therapeutics, using in vitro, ex vivo, or in vivo assays. This may include high, medium, or low-throughput assays, as well as counter-screening to assess the selectivity of hit and lead compounds.
• Design, synthesis, and preclinical testing of compounds directed toward altering, modifying, or regulating aspects of disease processes, as well as disease initiation or progression. This may include initial hit-to-lead chemistry to improve activity of compounds against the target of interest and/or later stage lead optimization to improve efficacy and pharmacokinetics.
• Development of ligands to serve as research tools in support of proof-of-principle preclinical studies and the validation of novel therapeutic targets.
• The isolation, identification, characterization, synthesis, and preclinical testing of promising naturally occurring products.
• Initial drug metabolism and pharmacokinetic (DMPK) and toxicity studies of candidate therapeutics. This may include in vitro and/or in vivo testing. IND-directed toxicology and safety pharmacology studies are outside the scope of this announcement.
• Use of innovative assays for the evaluation of the potential efficacy or toxicity of candidate therapeutics, such as cell-based or in vivo models systems that recapitulate critical molecular, cellular, or circuit/systems level features of a specific nervous system disorder, are encouraged. Preclinical assays should be directed toward assessing potential therapeutic benefit rather than elucidating disease mechanisms.  The choice of assays will be well-justified and appropriate for the stage of therapeutic development. While non-selective behavioral assays of CNS effects may be appropriate for initial in vivo preclinical screening, later stage in vivo assays used for candidate prioritization represent an opportunity to incorporate translational measures of circuits and brain processes linked to disorders.
• Development of novel delivery systems to target therapeutics to the brain.

The above-mentioned areas of investigation are representative and not meant to be exhaustive.

Deadlines for both:  standard dates apply

Filed Under: Funding Opportunities