You are here

Research Topics of Interest to NIDA

Description:

In this Omnibus Solicitation, NIDA emphasizes its need to discover, evaluate and develop medications (both small molecules and biologics) to treat substance use disorders (SUDs). NIDA further emphasizes an importance of fostering research through NIDA SBIR/STTR Program aimed at the research and development of medications for SUD, as well as research aimed at modernizing the drug discovery and development toolkit.

High programmatic priority will be given to research that seeks to achieve these goals in the following ways:

1)     Drug discovery and development-enabling activities: Development of innovative technologies, methods or tools, including but not limited to:

·       Innovative in vitro, in situ, or in vivo tools for the molecular analysis of the central nervous system, normal and/or diseased.

·       Tools to simplify drug design through the use of advanced computing (simulation) methods.

·       Development of pre-clinical models for addiction.

·       Creation of a data repository / software tools for addiction-related clinical research data.

·       Novel analytical technologies and methods that enhance the understanding of basic mechanisms of drug action and improve drug testing; technologies designed to overcome the performance limitations of current drug discovery and development tools.

·       Technologies, including molecular imaging, gene expression profiling, and genotyping and sequencing approaches designed to better inform the diagnosis and treatment of substance use disorders

2)     Drug discovery and development activities: Application of emerging and existing technologies and platforms to SUD drug development. This includes the identification, evaluation, development, approvability, and efficacy testing of new and improved pharmacotherapeutic agents, as well as the testing of marketed medications, and of behavioral treatments used alone or integrated with medications. Medical products with potential to minimize drug seeking, compulsive behavior, and/or addictive processes are strongly encouraged.

·       Chemistry / pharmaceutical drug development

·       Formulation and/or enhanced delivery of drugs

·       Preclinical and/or clinical drug development

·       Development of biomarkers related to treatment outcomes

Research Topics which are not aimed at development of medications for substance-use disorders or at modernizing the drug discovery and development toolkit, will have low program priority.

Specific projects could include:

Human Brain Neurochemical and Molecular Imaging. Measurement of brain neurochemistry, neuropharmacology (receptors) and gene expression in humans using non-invasive imaging has lagged behind advances in these areas in pre-clinical research as well as in functional and anatomical neuroimaging in humans. There is a continuing need for development of new ways to measure molecular targets in the human brain. Examples include, but are not limited to novel radioligands for PET and SPECT imaging in human brain for molecular targets (e.g., receptors, intracellular messengers, disease-related proteins), as well as novel methods that use magnetic resonance imaging or other emerging technologies such as optical imaging.. The primary application of these methods will be in basic human research. Ultimately, these measures may also be used as potential biological markers and surrogate endpoints for translational and clinical research, drug discovery and development, and clinical trials. The scope of the projects may encompass pilot or clinical feasibility evaluation in pre-clinical studies, model development, or clinical studies. Alternatively, the focus may be on research and development of new technologies for molecular, neurochemical or neuropharmacological development.

Steven Grant, Ph.D. 301-443-4877; Email: sgrant@nida.nih.gov

Development of Assays for "Designer" Drugs of Abuse Based on Pharmacologic Activity Rather Than Chemical Structure. Contemporary illicit drug chemists have turned to the pharmacology literature to produce new "designer" drugs of abuse including (but not limited to) synthetic cannabinoid analogues found in “herbal incense” mixes or substituted cathinone stimulants sold as “bath salts”. This new strategy has resulted in a diverse range of potential modified structures, all of which maybe pharmacologically active but each of which varies in molecular weight and substituents. This presents a substantial complication to traditional toxicology screens conducted in Emergency Rooms and to drug testing laboratories, whose assays rely on either immuno-assays or mass-spectrometry to detect specific agents. The current Funding Opportunity Announcement therefore aims to sponsor the development of assays based on pharmacologic activity rather than chemical structure.

Such assays should be:

·       Non-invasive and able to detect quantities of illicit materials or metabolites in a range of concentrations typically found biofluids of substance users within a few days of use.

·       Access to the biofluid samples should be minimally invasive and provide for temporal analysis. Such sample types include blood, urine, sweat and oral fluids.

·       Assays should be designed with a standard clinical or analytical laboratory in mind, i.e., to be analyzed in a high throughput format by technicians with a moderate scientific training.

·       The assays can be either designed to be analyzed with standard existing equipment, or include both the assay and development of analytical hardware, provided that the ultimate system can be commercially viable in a clinical and drug testing market place.

·       Assays should be designed to remain relevant as illicit substance chemists adapt to legislation by altering pharmacophoric substituents such as side chains. Examples of such assays would include (but be not limited to) scintillation proximity assays, robust cell-based assays to detect pharmacology rather than a particular chemistry, or cells expressing engineered receptors activated solely by synthetic ligands, designed to pick up a range of metabolites. Other examples might include microfluidic surface plasmon resonance devices, which can both concentrate and detect receptor or antibody-bound substances.

Aidan Hampson, Ph.D. 301-443-8039; Email: aidan.hampson@nih.gov

Discovery of New Chemical Probes.  SBIR applications are encouraged which propose to discover new chemical compounds as biological probes either by synthesis or isolation from natural resources in studying the mechanisms of action of drugs of abuse. Such substances could be new chemical compounds, drug products, or peptides. Currently there are several ligands available through the NIDA drug supply system such as SR 141716A, SR144528, CP 55,840, anandamide, epibatidine, Kaffiralin 1 and 2, etc. All probes for cannabinoids, neuropeptides, nicotinic acetylcholinergic receptors and related probes for drug abuse study are encouraged. In addition applications on biological screening of such new compounds as potential ligands for drug abuse research will also be considered.

Rao S. Rapaka, Ph.D. 301-443-1887; Email: rr82u@nih.gov

Nanoscience-based Design of Therapies for Substance Abuse Treatment.  Nanoscience and nanotechnology, by manipulating matter at the atomic or molecular levels, are emerging research areas that have the potential to fundamentally transform the study of biological systems and lead to the development of new methods for detection, prevention, and treatment of substance abuse and related disease states. NIDA invites nanotechnology-based applications in the following areas:

a.           Methods to enhance the efficacy of FDA-approved compounds by reducing their size to the nanoscale range to alter absorption, distribution, metabolism, or excretion.

b.           Development of new compounds, through manipulation of matter at the atomic or molecular levels that could more readily pass the blood-brain-barrier or cell membranes.

c.           Development of nanoscale particles for controlled targeted delivery of therapeutics, genes, or antibodies.

d.           Methods to enhance existing imaging technologies using magnetic properties at the nanoscale.

e.           Application of nanostructures (e.g. noble metal nanoparticles, quantum dots, and nanolithographic structures that show promise for diagnostic development) for identification and analysis of genes, proteins, and other biological molecules implicated in the actions of drugs of abuse.

Thomas G. Aigner, Ph.D. 301-435-1314; Email: ta17r@nih.gov

Drug Discovery – Chemistry and Pharmaceutics.  Within this area, NIDA supports research concerning the design (including molecular modeling and structure-activity relationship studies) and synthesis of novel compounds, formulation development, bioanalytical methods development, and pharmacokinetics/pharmacodynamics aimed at the discovery and development of novel medications for treating SUDs.

1.     Synthesis or discovery of new chemical or natural compounds that would have potential as treatment agents for the medical management of SUDs. Consideration should be given to the design of partial agonists or pure antagonists that diminish the reinforcing effects of stimulants, as well as full agonists that could function to normalize physiological activity following discontinuation of stimulant use.

       Compounds of interest particular include those that are designed to affect dopaminergic (e.g., D1 agonists, D3 agonists and D3 antagonists) activity, CRF antagonists, as well as those that affect glutamate activity, GABAergic activity, small molecule neuropeptide antagonists, and compounds acting through other mechanisms for which justification has been adequately supplied.

2.     Synthesis (either using traditional or combinatorial techniques) of new chemical compounds that would have potential as treatment agents for the medical management of cannabinoid abuse.

3.     Development of new immunotherapeutic treatments that would have the potential as treatment agents for stimulant or cannabinoid abuse.

4.     Development of heroin/morphine-protein conjugates (heroin/morphine conjugate vaccines) for the treatment of heroin/opiate addiction.

5.     Development of new approaches for the administration of potential addiction treatment drugs (including small molecules, natural products, peptides, proteins, antibodies, etc.) with poor bioavailability.

6.     Development of controlled-release dosage forms for addiction treatment medications in order to maintain therapeutic drug levels for extended periods of time to alleviate compliance problems associated with addiction treatment.

7.     Development of novel dosage forms or chemical/pharmaceutical approaches that eliminate or significantly reduce the abuse potential of prescription drugs/drug products.

8.     Development of novel technologies and strategies to enhance delivery of potential therapeutic agents across blood brain barrier for the treatment of SRDs.

Preclinical Drug Development.  Within this area, NIDA supports research on the development of preclinical behavioral models (e.g., of craving, drug-seeking behavior, dependence, or relapse), biochemical assays, gene expressional assays and electrophysiological methods to identify and characterize new medications to treat substance abuse, as well as pharmacological screening of novel compounds to identify potential drug abuse medications. This also supports research on toxicity studies of potential medications for the treatment of substance abuse, and interactions of potential treatment medications with abused substances. Areas that may be of interest to small businesses include, but are not limited to, development of new methods for discovery of medications useful in treating drug addiction. Of special interest would be the development of new animal models of addiction, incorporating established drug self-administration techniques that show increased relevance to the clinical setting. Development of relevant biochemical or electrophysiological screening methods is also encouraged.

Clinical Drug Development.  Within this area, NIDA seeks to support the clinical development of compounds that have completed (or are nearing completion of) successful preclinical evaluation of a novel pharmacotherapeutic- or immunological treatment(s) for persons with SUDs. Products can be evaluated in any Phase of clinical development, I, II, or III. Treatments should aim to help subjects become drug free, mitigate drug use, prolong abstinence/reduce craving, and/or facilitate survival from drug overdose. Whereas it is expected that all clinical trials testing a novel medication will provide a behavioral therapy component, the scope of this funding announcement does not provide for the evaluation of the safety and/or efficacy of psychosocial interventions.

Therapies that a small business might consider developing include, but are not limited to:

·       Repurposing of a compound developed for other indications (e.g., SSRIs, anti-epileptic drugs) that could be used to treat SUDs.

·       A novel (e.g., NCE, novel drug formulation) that could be used to treat SUDs

·       Vaccines for substances of abuse (e.g., cocaine, nicotine)

·       Monoclonal antibodies for substances of abuse (e.g., methamphetamine, PCP)

·       Naturally-occurring compounds (e.g., dietary supplements) that could be used to treat SUDs

·       Or, a rationalized poly-therapeutic combination of pharmacotherapies designed to more comprehensively treat SUDs

Treatments that concurrently help alleviate associated psychiatric co-morbidities (e.g., depression, schizophrenia, PTSD, anxiety, etc.) and/or are focused upon underserved/vulnerable populations (e.g., pregnant women and their fetuses, adolescents, racial or ethnic minorities, women/gender issues, subjects within the criminal justice system) are also encouraged.

Also of special interest are products that incorporate technological advances to more efficiently develop novel therapeutics for SUDs, such as:

1.           Improved methods to assess patient compliance during clinical trials (this can also include statistical modeling).

2.           Improved adjuvants to boost antibody responses to drugs of abuse.

3.           Discovery / development of biomarkers related to SUDs treatment outcomes. Because drug addiction is a brain disease which can change the structure and function of the brain, there is a unique opportunity to develop biomarkers that could reliably predict/assess SUD treatment outcome. To date, evaluations of SUDs often utilize subjective measures (e.g., patient-reported questionnaires) to assess disease progression and primary treatment outcomes. Biomarkers represent a more objective measure of physiological functioning that can be used to predict, diagnose, evaluate the progression of, and/or more accurately assess overall treatment safety and effectiveness. The goal of this initiative is to support the small business discovery/development of reproducible, quantitative biomarkers related to SUD treatment outcomes. Potential biomarkers might be derived from underlying variations in DNA, gene expression, proteins, metabolism, and/or neuroimages, among others. This solicitation is open to fast-track applications.

4.           Improved methods that can predict oral bioavailability of drug-like substances (in vitro; in vivo, in silico). For example, this might include the development of an innovative test /device that can be used to help more effectively diagnose and/or manage patients with SUDs. The use of this novel diagnostic tool might help to: (a) expedite the development of-, and/or (b) enhance existing treatments for patients with SUDs. Possible diagnostic tests/devices that a small business might consider, but are not limited to, include:

o   An assay/device (e.g., skin sensors, oral swabs) that detects a substance of abuse more reliably than oft-used urinalysis. Optimally, the analytical test/device would be non-invasive and easy-to-use, such that it could be used on an outpatient basis.

o   Discovery/development of a diagnostic test/screen that could help physicians more effectively manage treatments for patients with SUDs.

Kristopher Bough, Ph.D. Tel : 301-443-9800; Email: boughk@mail.nih.gov

US Flag An Official Website of the United States Government