Reissue of PAR-19-289 - Building in vivo Preclinical Assays of Circuit Engagement for Application in Therapeutic Development (R01 Clinical Trial Not Allowed)
NOT-MH-22-210 - Notice of Intent to Publish a Funding Opportunity Announcement for Novel Assays to Address Translational Gaps in Treatment Development (UG3/UH3 Clinical Trial Optional)
National Institute of Mental Health (NIMH)
The National Institute of Mental Health (NIMH) intends to publish a Funding Opportunity Announcement (FOA) to solicit applications to identify, in animals, in vivo neurophysiological and behavioral measures for use as assays in the early screening phase of treatment development. This FOA will be a reissue of PAR-19-289.
This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.
The FOA is expected to be published in Spring 2022 with an expected first application due date of October 5, 2022.
The FOA will utilize the R01 activity code. Details of the planned FOA are provided below.
Consistent with the objectives of PAR-19-289, studies appropriate for the FOA will optimize and evaluate measures of neurophysiological and behavioral processes that may serve as surrogate markers of neural processes of clinical interest based on available knowledge of the neurobiology of mental illnesses. The screening assays thus developed from the FOA are expected to build upon systems neurobiology and clinical neuroscience to enhance the scientific value of preclinical animal data contributing to a therapeutic development pipeline by assessing the impact of therapeutic targets and treatment candidates on neurobiological mechanisms of clinical relevance to mental illnesses.
The objectives of the FOA will be accomplished by supporting basic and translational neuroscientists who are committed to improving the efficiency and scientific value of the therapeutic development pipeline by advancing the discovery of in vivo physiological and behavioral measures reflecting circuit engagement as tools for early phase target validation and therapeutic screening for mental illness treatment development. The efforts supported by the initiative focus on measures in animals as a first step in generating translational assay measures that are adaptable across early therapeutic screens in animals to evaluation in humans. The FOA may be considered a prequel to build a suite of assays that are evaluated in future projects for coherence of assay performance between the preclinical species and healthy humans. The FOA will support efforts to improve the tool kit of assays available for early phase testing of novel therapeutic agents by incorporating measures proximal to neural systems that impact mental health.
The FOA supports the initial stages in the development, optimization, and evaluation of novel in vivo measures as potential assays in early (pre-first in human) screening of therapeutic candidates. Assays may include neurophysiological and/or behavioral measures. Key considerations are listed below but at a minimum, measures should be amenable to study in live animals and in future studies in humans, and they must be innovative.
Priority will be given to applications that include all three of the following phases:
Support will be provided for assay development efforts in animals that propose quantitative measures of neurophysiological and/or behavioral processes where there is reasonable evidence to suggest that measure is a potential contributor to functional deficits of individuals with mental illnesses (e.g., cognitive function, impulsivity, and motivation, etc.).
Examples of relevant neurophysiological and/or behavioral measures for development and evaluation as assays include, but are not limited to:
Mechanistic testing of underlying brain pathways will be tailored to the proposed assay measure. For example, studies might examine if specific changes in dopamine signaling to striatum or prefrontal cortex reliably predict speed or accuracy of reward contingency learning. These studies are critical for advancing a new generation of in vivo assays for therapeutic development that are be grounded in a clinically-meaningful neurobiological context.
The main emphasis must be on developing novel, clinically relevant measures as assays. While the neurophysiological or behavioral measures may not be innovative by themselves, their inclusion in a therapeutic development pipeline must be novel.
Since this work is expected to identify and optimize novel assay measures that can subsequently be compared with measures in healthy humans, it is imperative that proposed neurophysiological and behavioral assay measures be feasible to perform in healthy humans.
Application budgets are not limited but need to reflect the actual needs of the proposed project. It is expected that budgets of $250,000 direct costs per year or less will be adequate for most projects proposing to optimize just one measure.
Applications are not being solicited at this time.
Please direct all inquiries to:
National Institute of Mental Health (NIMH)