HHS SBIR PA-09-045

Background

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, might benefit from constellations of several different biomarkers being used in concert. 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, and show the response of a disorder to a given treatment. Such information would have clear and significant clinical benefit, and are urgently needed.

The National Institute of Mental Health (NIMH) supports research on mental disorders including schizophrenia, depression, bipolar disorder, attention deficit hyperactivity disorder, anxiety disorders, eating disorders, Tourettes syndrome, obsessive compulsive disorder, autism spectrum disorders, AIDS dementia complex, etc. Some disorders appear as a broad spectrum where signs and symptoms vary enormously but yet collectively represent one general disorder (e.g., autism spectrum disorders). In other instances, a particular symptom may appear across a variety of mental disorders (e.g., cognitive impairment) or represent an exaggeration of a dimension seen in healthy individuals (e.g., depressed mood). It is possible that biomarkers could aid clinicians in categorizing particular signs and symptoms so that a spectrum disorder could be broken down into well-defined subcategories, allowing differential analysis or treatment. Biomarkers could also be used to clarify boundaries between health and illness, and could be used in basic research to map the variability of a marker across healthy populations.

Goal

The goal of this initiative is to support small businesses to develop innovative biomarker technologies, with commercial potential, for clinical and/or basic research utility, with the long term, but clear, objective of their being used in humans to assess mental function and dysfunction as related to mental illness.

Research Activities and Examples

There are many approaches a company could take to commercialize a biomarker. Examples of types of products include: in house services, heterogeneous databases that include biomarker data combined with behavioral, clinical or other functional data, toolkits that enable other researchers to use the biomarker with appropriate hardware, software, or wetware needed to carry out the study, development of a novel detection system for measuring a particular biomarker, development of a marketable protocol for measuring a biomarker, novel technologies that enable new biomarkers to be identified, etc. Identifying, parameterizing, optimizing and validating the use of particular biomarkers with regard to their relationship to brain or behavioral function are among the research activities encouraged by this program announcement. Projects limited to basic research on biomarkers with no clear path to developing these for use in humans are not encouraged by this program announcement (though early stage research in animal models is appropriate).

The NIMH is specifically interested in clinically applied biomarkers as well as those useful in basic brain or behavioral research. In all cases the biomarker should be effective on an individual basis, rather than from pooled individuals. Also, biomarkers appropriate for this program announcement may be intended to be used with behavioral measures, but behavioral measures alone are not considered biomarkers here. Biomarkers could be noninvasively obtained (e.g., using optical or magnetic resonance imaging, etc.) or obtained with minimal invasiveness (e.g., using genetic, protein or metabolic signatures, physiological measures, etc.). NIMH is interested in biomarkers that are useful across the lifespan as well as those that are useful for particular age groups (e.g. infancy, childhood, adolescence, adulthood, elderly).

Specific examples of clinical applications include: reliable and stable biomarkers that can identify at-risk individuals prior to disease onset, biological and behavioral indicators or predictors of treatment response, measures of disease progression, measures to identify dose ranges prior to clinical studies, preclinical or clinical efficacy testing, toxicity measures for drug development, defining patients to enroll in the clinical study, identifying CNS abnormalities, etc. It is important to note that these examples are merely illustrative and are not meant to limit the scope of appropriate clinical applications.

Specific examples of basic research applications: biomarkers 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, etc. 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 basic research applications.

NIMH-Wide Interest

All of the divisions at NIMH have interests in biomarker development. Therefore, Dr. Margaret Grabb will be an initial point of contact for the institute and will refer potential applicants to the most appropriate program contact in the most appropriate division.

NCCAM is also inteerested in applications proposing studies on stress.

Possibility for SBIR Type 2 (Renewal) Phase II Competing Renewal Support

If a company is proposing to develop biomarkers as diagnostic tools, and requires Federal Regulatory Approval prior to commercialization, the company may be eligible for a one time SBIR Phase II Competing Renewal Award after receiving a previous Phase II award. Potential applicants should contact Dr. Margaret Grabb (see Section VII), and she will refer the company to the appropriate division for additional information in this regard.