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The overarching goal of the SBIR program at the National Institute of Mental Health (NIMH) is to support small businesses to develop technologies that can advance the mission of the Institute, including in basic neuroscience research relevant to mental disorders, translational and clinical research of mental disorders, clinical diagnosis or treatment of mental disorders, and dissemination of evidence-based mental health care. The NIMH Strategic Plan (http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml) presents key scientific priorities across these domains, and describes the need for tools to realize these priorities. Research priorities for the NIMH further include aspects of HIV/AIDS prevention, treatment, and care, in accordance with the Trans-NIH Plan for HIV-Related Research (http://www.oar.nih.gov/strategicplan/).
The SBIR program is one source of support for the research and development of technologies that correspond to these identified research priorities. While some tools can be developed with budgets and project durations within the standard SBIR guidelines, others cannot. This FOA encourages SBIR applications for support of research and development of particular types of technologies that require funding levels and durations beyond those reflected in the standard SBIR guidelines. For additional tools in which NIMH is interested, but which can be supported within the standard SBIR guidelines, see the NIMH-related topics of the SBIR Omnibus Solicitation - PAR-11-096.
Applications submitted in response to this FOA are expected to represent significant advances and innovation.
Biomarkers and Biosignatures of Mental Illness:
Biomarkers are objective, measurable biochemical, genetic, or other biological indicators of a physiological or disease process. While some individual biomarkers are useful in biomedicine, complex conditions such as mental illness (including HIV-related neurological and neuropsychiatric impairment) might benefit from constellations of several different biomarkers being considered together (i.e., biosignatures). Whether used alone or in conjunction with others, biomarkers could facilitate definitive diagnosis of mental disorders in individuals, assess the susceptibility of individuals to a particular disorder, indicate changes in the severity of a disorder, show the response of a disorder to a given treatment, or the likely responsiveness of a particular patient to a given intervention. Biomarkers and biosignatures would have clear and significant clinical benefit, and are urgently needed. NIMH is specifically interested in supporting the development of clinically applied indicators as well as those useful in basic brain or behavioral research. Ideally, these would be noninvasively obtained (e.g., using optical or magnetic resonance imaging, etc.), or obtained with minimal invasiveness (e.g., from body fluids using genetic, protein or metabolic signatures, physiological measures, etc.). Specific examples of clinical applications include: reliable and stable biomarkers that can identify at-risk individuals prior to disease onset, biological and behavioral indicators of treatment response, measures of disease progression, to identify dose ranges prior to clinical studies, to define patients to enroll in the clinical study, to identifying CNS abnormalities, etc. Specific examples of basic research applications: indicators that enable refined assessment of normal and atypical infant, child and adolescent brain development and brain function, biomarkers for assessing changes in specific mental functions over the lifespan. Either human subjects or relevant animal models would be appropriate to use in basic research applications. It is important to note that these examples are merely illustrative and are not meant to limit the scope of appropriate applications.
Drug Discovery/Drug Development in Mental Illness:
Through the SBIR program, NIMH continues to support the development of pharmacologic agents that target novel molecular entities, relevant to mental health disorders, or domains of function (e.g. cognitive function). In the last decade, only a relatively small number of drugs have been approved for the treatment of mental health disorders, and most were chemically based on older marketed compounds. In addition, none specifically targeted neurodevelopmental epochs at which a mental health disorder’s symptoms may begin to appear. The lack of such compounds not only may be limiting the utility of such interventions for pediatric populations, but may also be missing a key juncture at which intervention might have particularly long-term benefits. NIMH is specifically interested in supporting the development of pharmacologic agents, based on novel molecular CNS targets that improve function and minimize the side effects seen with current medications. In addition, compounds targeted for the treatment of pediatric mental health disorders would also be of interest. SBIR support in drug discovery/development is broad and ranges from the development of novel ligand screening assays (such as computational, high throughput, genetic, molecular/cellular, or whole animal) to novel chemistry approaches, to lead compound identification/optimization preclinical efficacy, IND-enabling studies, and up to FDA Phase I and II clinical trials. Novel clinical trial designs/approaches would also be applicable, if well justified.
An additional focus in this area is the support of technologies that would enable researchers to selectively screen for compounds with high selectivity to Central Nervous System (CNS)-located G-protein coupled receptor proteins (GPCRs). Many of the GPCRs have potential significance in healthy mental function and in mental disorders, including receptors for serotonin, glutamate, dopamine, opioids, GABA, orexins, somatostatin, muscarinic, cannabinoid, adrenergic, Neuropeptide Y, corticotropin releasing factor (CRF) and others. Drugs targeting GPCRs are currently used in the treatment of mental health disorders such as schizophrenia, anxiety and depression. Yet identification or synthesis of selective agonists and antagonists to these particular receptor subtypes has proved daunting, due to the current lack of knowledge about the three dimensional (3-D) structure of many of these receptors, and their diffuse brain distribution. , Therefore, this FOA encourages the development of technologies to aid in the identification of their 3-D structures or in some other way, enable researchers to selectively screen for compounds with high selectivity to the receptor (and minimize side effects). Technologies and approaches aimed at either known receptor subtypes or orphan receptors would be of potential interest.
Therapeutics Development for HIV/AIDS-Associated Neuropsychological Disorders:
The NIMH Division of AIDS Research (DAR) encourages SBIR applications targeting the discovery and development of novel therapeutic agents, methods, biomarkers, and drug delivery technologies that can address the neurological implications of HIV infection and seek to directly or indirectly eliminate/eradicate HIV reservoirs in the brain. The overriding focus is upon the development of adjunctive therapies against the consequences of HIV in the central nervous system, but novel assays/models of neurotoxicity and treatment efficacy measures are also invited, as well as novel in vitro/vivo models that can be used for screening potential therapeutic agents.
Development of PET and SPECT Ligands for Brain Imaging:
This topic is intended to stimulate the development of radioligands for CNS- relevant molecular targets (e.g., receptors, cell adhesion molecules, intracellular messengers, and disease related proteins) that are of interest to the mental health scientific community. The widespread availability and use of these radioligands are expected to: 1) accelerate research on identifying and characterizing the neural circuits and pathways implicated in the pathophysiology of psychiatric brain disorders and HIV-associated neurological and neuropsychiatric impairment, and 2) facilitate the identification of new therapeutic targets and the development of new compounds as potential therapeutic agents. Research support under this topic includes: lead compound identification, preclinical studies, IND-enabling studies, pilot human imaging studies in normal volunteers and clinical studies in psychiatric populations.
Tools to Facilitate Mental Health Research:
The complexity of conducting and managing mental health research is significant due to the diverse technologies/methodologies currently being used, difficulty in the recruitment of subjects, broad categorical diagnoses of disorders, unique cultural and developmental aspects of a disorder, etc. Therefore, the NIMH seeks the development of innovative technologies/strategies to help mitigate some of these issues.
Examples could include one or more of the following: technologies to improve clinical research recruitment, patient and doctor compliance, clinical trial design or implementation; the application of technology to enhance the science, operation, and management of large or multi-site mental health or HIV/AIDS clinical trials; the development of innovative computer-based observation techniques, and computer software and hardware that facilitate screening, assessment and monitoring during clinical trials; the development of portable clinical trial management systems such as serious adverse event (SAE) oversight and monitoring software; advanced methods to visualize complex clinical and biological data; development of real time risk assessments or a clinical tool that enables clinicians to quickly recognize a change in patient health and therefore improve clinical care.
The NIMH is also supportive of the development and implementation of robust rapidly scalable data systems that can safely and efficiently import and house core data from multiple independent sources (i.e. large health care providers) and from different hardware platforms. Such systems would effectively categorize, merge and aggregate data from multiple independent sources and would utilize a core data element structure. This system would enable researchers to easily access the system, identify potential research subjects, analyze clinical data, produce reports and “data mine.”
Tools/Platforms to Improve the Dissemination and Implementation of Evidence-Based Mental Health Interventions:
Clinical mental health research produces a vast amount of information that should be informative to mental health care providers, yet there are no easy ways for this information to be transformed into standard clinical practice. Similar concerns have been noted with regard to advancing the uptake and sound implementation of efficacious HIV prevention and care interventions by HIV providers, clinics, and community-based organizations.
The NIMH supports the development of innovative user-friendly tools and platforms to efficiently and effectively disseminate evidence-based treatments/research into services and clinical practice. Such tools may incorporate applied behavioral science and technology, software, hardware and associated technologies. The focus of the information being disseminated might include: the development of strategies or tools to assist mental health care providers in detecting and monitoring mental illness progression, in implementing proven interventions, or in predicting treatment response and vulnerability to side effects of psychotropic medications. Systems may also seek to advance the identification, dissemination, adoption, or effective implementation of evidence-based behavioral interventions for HIV prevention and care.
Additional NIMH interests include the development of geographic based systems (GIS) that can identify disparities in mental health treatment and demonstrate the impact of the effective dissemination of proven mental health treatments across and within geographic areas. The NIMH holds further interests in data translation and communication packages for collecting, archiving, and safely and securely making available existing mental health and HIV/AIDS data sets to the scientific community for secondary or meta-analyses. It is expected that the dissemination platform be state of the art, considering the latest electronic technologies, so as not to develop a tool that becomes obsolete during the commercialization phase. In addition, dissemination of interventions that have not been well-validated would not be appropriate for commercialization.
Mental disorders are increasingly seen as developmental disorders. The potential to harness neuroplasticity -- to enhance the ability of the nervous system to reshape and form new connections -- may be the basis for therapeutic approaches to disorders such as post-traumatic stress disorder, and cognitive impairment. Thus, understanding neural development and plasticity at all levels, from molecules and cells to circuits and behavior, has broad implications for mental health. The NIMH SBIR program continues to support the development of tools or techniques that will significantly advance the current state of the art in neuroplasticity research. Although applications will not be restricted to developing a particular type of technology, we are especially interested in applications that seek to harness the ability to assess and manipulate activity with exquisite subcellular resolution, and in cells specified by their circuit connectivity and/or transmitter phenotype. Examples include: new or enhanced reporters of neural activity, novel tools for manipulating neural circuits, and improved imaging equipment.
The NIMH has a longstanding interest in developing and seizing the promise that digital approaches hold for brain and behavioral research, and for advancing the understanding, prevention, and treatment of mental disorders. In accord with that interest, grant applications are sought from small businesses that propose to develop and validate novel, commercializable, computational tools and resources that will aid neuroscientists, mental health researchers, or mental health providers in their research or practice. Examples of appropriate applications range from computational models for drug discovery in mental health disorders or HIV-associated CNS disorders, to ones that combine genetic, biological, behavioral and environmental factors to assess pediatric vulnerability to mental disorders, to methods to enhance efficiency of early phase clinical trials. These examples are not meant to be exclusive.
Many of the common technologies used in neuroscience and behavioral science research require extensive time, labor, and cost for acquiring and analyzing data. With many significant advances in technical areas including computer vision, molecular biology, robotics, nanotechnology, microarray fabrication, imaging, etc. occurring over the last decade, combined with discoveries in neurobiology, a unique opportunity is available to bring these technology and biomedical areas together to develop innovative high throughput tools relevant to brain and/or behavior. Applications considered appropriate to this topic would include those proposing research and development of tools for high throughput measures at any level (or combination of levels) of analysis: from genes and molecules through behavior, including cognition and social behavior. The tools would, of course, need to be aimed at rapid acquisition and analysis of data, such as the collection of CNS physiological data from multiple subjects at one time. While the range of measures by tools is wide, appropriate applications must propose research and development of tools that would significantly improve the ability to rapidly acquire data from multiple experiments simultaneously, and rapidly analyze the collected data.
Nanotechnologies are showing promise in diverse roles highly relevant to NIMH priorities. In particular, NIMH is interested in nanotechnologies that focus on a variety of technologies including: the development of extended release formulations of psychiatric drugs, biomarker assays, probes for microimaging, in vitro assays to study neuronal function, and assays to allow GPCR function to be studied. NIMH is further interested in nanotechnology to address HIV-associated neurological and neuropsychiatric impairment, particularly with regard to the delivery of antiretroviral medications or neuroprotective compounds across the blood-brain barrier.
An additional criteria that the federal government considers in supporting a small business with SBIR funds, is past commercialization performance. It is expected that small businesses who have received many SBIR grants, have made significant effort to commercialize their previously supported technologies. Small businesses that are mostly interested in research and development (and not commercialization) should consider other grant mechanisms at NIH, rather than the SBIR program. Program staff at NIMH can help identify the most appropriate grant mechanism to use.
Additional information about NIMH research interests may be found here:
1) NIMH Strategic Plan: http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml
2) NIH SBIR website: http://grants.nih.gov/grants/funding/sbir.htm