Extracellular Vesicle Tools, Technologies, and Products for Neuroscience Research (R41/R42)

Secreted extracellular vesicles (EVs) play roles in myriad biological processes including neuronal function.  In some cases EVs appear to travel through the body and fuse with specific cell types to deliver nucleic acid, protein or other cargoes that may alter cellular phenotypes and functions.  In the nervous system, EVs may function in neuronal-glial communication, synaptic plasticity, and/or immune surveillance.  However the role of EVs in psychiatric disorders and substance abuse is not well characterized. 

In addition, EVs from body fluids such as blood, cerebrospinal fluid, urine, saliva, semen, breast milk, and amniotic fluid could provide useful biomarkers for a variety of human diseases including brain disorders.  Understanding EV dynamics and cargoes across the trajectory of addiction may help to identify useful biomarkers for diagnosing: 1) drug use history (the type, quantity, and/or frequency of drug use), 2) the stage/trajectory of drug addiction (e.g. escalation, withdrawal, incubation, craving, relapse), or 3) both.  Also EVs could be useful for in vivo targeting of cargoes (e.g. nucleic acids or small molecules) of therapeutic value to specific organs or cell types.

Despite the growing interest in and importance of EVs for mechanistic, biomarker, and therapeutic projects in the area of neuroscience, the currently available EV tools are limited.  The purpose of this initiative is to incentivize small businesses to develop tools, technologies, and products enabling research scientists to exploit EVs for neuroscience research.  In the long term, it is hoped that these tools and products will serve as the foundation for NIDA-relevant mechanistic, diagnostic, and therapeutic studies in the area of EV communication and drug addiction.

With respect to scope, proposed projects must address the following:  1) the major thrust of the application should involve EVs, EV-associated secretory machinery, or protein/RNA complexes in body fluids; 2) the applicant must describe how the commercialized product could be applied by researchers to explore EV mechanisms, identify biomarkers, or serve as the foundation for developing future treatments for brain disorders including addiction to substances of abuse, and 3) applications developing biomarkers must focus on substance use disorder or HIV-relevant phenotypes.  Applications that do not adhere to these three criteria will not be responsive to this FOA and will not be reviewed. 

Two companion FOAs have been released in this scientific area:  RFA-DA-17-009 describes the SBIR R43/R44 mechanism, while this FOA (RFA-DA-17-008) describes the STTR R41/R42 mechanism.  If the innovative tool to be commercialized will be developed via a partnership of ideas between a small business and an academic/non-profit research institution, the program director/principal investigator should consider applying using the STTR mechanism (R41/R42).  Otherwise, small businesses interested in the development of relevant innovative tools, technologies or products are encouraged to apply via the SBIR mechanism (R43/R44).  Applicants are encouraged to contact NIH Scientific/Research staff for more detailed guidance. 

Examples of Potential Tools, Technologies, or Products. This initiative will support small business development of tools, technologies, or products such as:

Purification and Characterization

• commercialization of products or kits that enable identification and isolation of brain-specific, neural-specific, glial-specific, or cell type-specific vesicles from body fluids (e.g. serum, cerebrospinal fluid, urine, saliva, semen, breast milk, or amniotic fluid)
• commercialization of products or kits for characterizing EV classes, cargoes, target cells, or functions
• commercialization of products or kits that improve our ability to characterize one or more EV cargo types (e.g. RNA, protein, lipid, metabolite)
• commercialization of software or bioinformatics pipelines that improve our ability to analyze EVs or EV cargo data
• tools or products that could help researchers better explore the role of EVs or EV secretory machinery in neuroplastic processes such as addiction
• tools or products that could help researchers better explore EV function in the nervous system with respect to neuronal-glial or CNS-immune interactions
• commercialization of products or kits to enable isolation or characterization of protein/RNA complexes in body fluids

Biosignatures for Chronic Drug Exposure or Addiction Trajectory

• the development of EV-based biomarkers (including EV RNA, protein, lipid, metabolite or other cargoes) to help assess chronic drug exposure, addiction trajectory, recovery from addiction via medications or behavioral therapies, or other addiction-relevant phenotypes
• the development of EV-based biomarkers (including EV RNA, protein, lipid, metabolite or other cargoes) to help assess HIV levels in brain.

Neurotherapeutics

• commercialization of products to exploit natural or artificial extracellular vesicles to deliver therapeutic cargoes across the blood brain barrier, to specific brain regions, and/or to specific CNS cell types

Special Considerations

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse:  In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing.  NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV.  This policy applies to all NIDA funded research conducted domestically or internationally.  For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects:  The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects.   Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects.  The guidelines are available on NIDA's Web site at  http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community.  Please see http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit:  NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org).  Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.   

See Section VIII. Other Information for award authorities and regulations.