NIAAA supports research on the causes, prevention, control, and treatment of the major health problems associated with alcohol use. Through its extramural research programs, NIAAA funds a wide range of basic and applied research to develop new and/or improved technologies and approaches for increasing the effectiveness of diagnosis, treatment, and prevention. NIAAA also is concerned with strengthening research dissemination, scientific communications, public education, and data collection activities in the areas of its research programs.

NIAAA Non-clinical Research Topics

Medications Development

Pharmacotherapy offers a promising means for treating AUD. Currently, there are four Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of AUD: disulfiram (Antabuse®), oral naltrexone (Revia®), acamprosate (Campral®), and the injectable suspension formulation of naltrexone (Vivitrol®). Another medication, nalmefene (Selincro®), has recently been approved by the European Medicines Agency (EMA). However, given the heterogeneous nature of AUD, many patients have limited or no response to the aforementioned medications. Because of this, developing and evaluating new, more efficacious medications remains a high priority.

During the past five decades, alcohol research has enriched our understanding of the biological mechanisms underlying AUD. Various neurotransmitter systems, neuromodulators, and intracellular signaling pathways have a role in AUD. To date, more than 35 promising targets have been shown to alter alcohol drinking behavior. Some of the new promising targets include, but are not limited to, corticotrophin-releasing factor1 (CRF-1), adrenergic α1 and α2, vasopressin 1B, orexin 1 and 2, opioid receptor-like (NOP), opioid kappa, 5-HT2, GABA-A and GABA-B, metabotropic glutamate (mGluR), glutamate transporter (GLT), nicotinic acetylcholine (nAChR), phospodiesterase (PDE), glial derived neurotrophic factor (GDNF), and neuroimmune and epigenetic modulators. New medications that bind to these and additional targets are needed.

Candidate medications may include novel and re-purposed compounds.  Specific areas of interest include medications that target one or more domains of the addiction cycle, including reward, stress and negative affect, incentive salience, executive function, habituation, and impulsivity/compulsivity.

For questions, contact:

Raye Z. Litten, Ph.D.
Telephone: 301-443-0636
Email: Raye.Litten@nih.gov

Additional targets for pharmaceutical development include, but are not limited to agents that attenuate excessive alcohol use and other symptoms of AUD, e.g., craving, sleep problems, and negative affect as well as those that hold promise for the treatment of alcoholic hepatitis, liver fibrosis, cirrhosis, pancreatitis, cardiomyopathy, or other alcohol-induced tissue damage.

For pre-clinical questions, contact:

Mark Egli, Ph.D. (Neuroscience and behavior)
Telephone: 301-594-6382
Email: Mark.Egli@nih.gov

Svetlana Radaeva, Ph.D. (Organ damage)
Telephone: 301-433-1189
Email: Svetlana.Radaeva@nih.gov

Technological Methods for the Treatment of Hazardous Drinking and Alcohol Use Disorder

  • Develop, improve, and validate ecological momentary assessment (EMA) methods for capturing real-time data for use in alcohol clinical trials and treatment paradigms.
  • Use technology (e.g. EMA, brain imaging) and innovative statistical methods (e.g., machine learning, systems science dynamic models) appropriate for analysis of “big data” (i.e., time intensive, multisource data) to inform our understanding of mechanisms underlying the initiation, maintenance, and recovery from problematic drinking in both treatment and naturalistic settings. Leverage unique features of mobile technologies to provide personalized monitoring and just-in-time interventions including but not limited to a variety of racial/ethnic and linguistic populations.
  • Optimize existing technologies to increase their utilization and effectiveness in specific treatment contexts (e.g., primary care) and improve patient-provider communication to decrease harmful drinking including across racial, ethnic and linguistic groups.
  • Develop and test computerized versions of empirically-supported treatments, including but not limited to in languages other than English.
  • Develop and test novel computerized interventions which capitalize on hypothesized brain-based or behavioral mechanisms underlying drinking
  • Develop software to train potential treatment professionals on how to provide evidence-based treatments
  • Devise novel methods (e.g., Web-mining software of social networking sites) that capture social network information among groups at risk for alcohol use disorder and high-risk drinking, including but not limited to racial and ethnic minority populations.
  • Develop and test the efficacy of neurophysiological treatment approaches such as transcranial magnetic stimulation, neurofeedback, and deep brain stimulation.

Anita Bechtholt, Ph.D.
Telephone: 301-443-9334
Email: anita.bechtholt@nih.gov

Prevention

This area of interest focuses on the development and evaluation of innovative prevention and intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Applicants are strongly encouraged to consult with research methodologists and statisticians to ensure that state-of-the-art approaches to design, analysis, and interpretation of studies under this topic are used. Areas that may be of interest to small businesses include, but are not limited to:

  • Development and evaluation of innovative prevention/intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Special emphasis should be placed on the needs of high-risk groups, ethnic and minority populations, youth, children of individuals with alcohol use disorder, women, the handicapped, sexual and gender minority populations, and the elderly. Examples of such materials include school-based curricula, interactive videos, computer-based multimedia programs, training manuals for teachers or parents, and community-based programs.
  • Development and evaluation of educational materials designed to intervene with the elderly around specific age-related risks for alcohol problems. Particular attention should be given to age-related reductions in alcohol tolerance, interactions between alcohol and prescription and over-the-counter medications, possible exacerbation of some medical conditions common among the elderly, potential biomedical and behavioral consequences of excessive alcohol use, and the role of alcohol in falls, fires, burns, pedestrian and traffic injuries, and other unintentional injuries.
  • Development and evaluation of statistical analysis programs tailored to the design and analysis of alcohol prevention-relevant research. Programs could focus on a variety of areas including: imputation of missing data under varying design assumptions; development and application of statistical models suited to small sample sizes common in racial and ethnic minority research; simulation of distributions of outcomes based on varying mixtures of sample populations; application of chronic or infectious disease models to targeted communities; and models of the potential effect of various policy-based interventions, such as increased taxation or reduction of outlet density by license revocation and control.

Robert C. Freeman, Ph.D.
Telephone: 301-443-8820
Email: Robert.Freeman@nih.gov

Improving the Delivery of Alcohol Treatment Services

NIAAA’s treatment services research program studies the organization, management, and financing of alcohol treatment services, and how these affect service availability, access, utilization, cost, and quality. Needed innovations in this area include the development of state-of-the-art technologies, software, and protocols to expand and improve the delivery of evidence-based treatment for alcohol use disorder.

Areas that may be of interest to small businesses include, but are not limited to, the development and assessment of software or tools to:

  • assist clinicians in selecting and delivering evidence-based treatments consistent with patient needs and available staff and program resources across racially, ethnically and linguistically diverse populations. Special attention should be paid to promoting fidelity of treatment delivery in real-world contexts. For example: software to enable the creation or use of clinical decision support systems, screening protocols, or patient registries; prescription medication management tools; scripts or guides for delivery of brief interventions; and interactive training resources.
  • support long-term recovery, by facilitating patients’ continued engagement in recovery support services as an adjunct to or after treatment. For example: software to assist patients in self-management and self-monitoring of drinking behaviors, cues, or triggers, and/or in locating treatment resources or recovery support services.
  • assist treatment programs and service agencies in measuring clinically relevant performance indicators or improvements in quality of service provision.
  • promote engagement and mitigate burnout among counselors and others engaged in direct treatment service delivery. Tools are needed to reinforce training on therapeutic techniques; provide minimally-obtrusive methods for monitoring and enhancing fidelity of service delivery; engage counselors in mindfulness or other strategies to manage job stress and reduce burnout; and provide front-line counselors with supports essential to maintaining productive therapeutic relationships with patients.

Laura Kwako, Ph.D.
Telephone: 301-451- 8507
Email: laura.kwako@nih.gov

Fetal Alcohol Spectrum Disorders (FASD) and Alcohol-Related Birth Defects

FASD is the collective term for the broad array of adverse effects resulting from in utero alcohol exposure. Fetal alcohol syndrome (FAS), the first form of FASD discovered and the most well-known, is characterized by craniofacial abnormalities, growth retardation, and nervous system impairments that often include intellectual disabilities. Other diagnostic categories include partial FAS, alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). Children and adults with FASD may exhibit multiple cognitive, behavioral, and emotional deficits that impair daily functioning in many domains. The NIAAA supports research leading to improved diagnosis and assessment of prenatal alcohol exposure and related impairment and disability, as well as the development of therapeutic interventions, including tools to enhance academic and daily living skills across diverse racial, ethnic and linguistic populations. Areas that may be of interest to small businesses include, but are not limited to:

  • Development and assessment of diagnostic and/or screening methods, tools, or technologies to improve earlier identification of individuals affected by prenatal exposure.
  • Development and validation of biomarkers that can be used to verify prenatal alcohol exposure in neonates or predict those individuals with neurobehavioral deficits later in life.
  • Development and validation of assessment methods to provide more accurate clinical diagnosis of FASD at all life stages.
  • Development and testing of skill-building, therapeutic, and education program products that enhance the social, cognitive, adaptive and motor abilities of individuals with FASD.
  • Development of neurobehavioral tools or instruments to assess responsiveness of individuals with FASD to medications and/or cognitive/behavioral therapies.
  • Development of accurate measures of the responsiveness of children affected by prenatal alcohol exposure to stress and predictors of vulnerability to alcohol-drinking or other psychopathology during adolescence and adulthood.
  • Development and evaluation of educational and training programs designed to enhance the skills of non-professional caregivers in dealing with the problems associated with FASD.
  • Development and validation of innovative methods, tools or technology to prevent harmful drinking during pregnancy.

For basic research questions, contact:

William Dunty, Ph.D.
Telephone: 301-443-7351
Email: William.Dunty@nih.gov

For prevention research questions, contact:

I-Jen Castle, Ph.D.
Telephone: 301-827-4406
Email: i-jen.castle@nih.gov

Deidra Roach
Telephone: 301-443-5820
Email: Deidra.Roach@nih.gov

Development of Clinical Biomarkers of Alcohol Exposure and Alcohol-Induced Organ Damage

There is a well-recognized need for prognostic and diagnostic biomarkers of alcohol exposure, for biomarkers of the response to clinical treatment, and for biomarkers to monitor abstinence in high-risk individuals. Quantitative and qualitative markers of high-risk drinking behavior and alcohol-induced tissue damage would greatly improve medical efforts to recognize and treat alcohol-related disorders. Currently, no clinically available laboratory test can reliably diagnose duration of alcohol use or predict the progression of alcohol-induced organ damage. Traditional alcohol biomarkers fail to provide long-term information. More recently developed alcohol biomarkers (ethanol metabolites phosphatidylethanol (PEth), ethyl glucuronide (EtG) and ethyl sulfate (EtS)) display improved sensitivity, specificity, and accuracy over classical biomarkers. Their useful range of a few days (EtG) to 2-4 weeks (PEth) addresses many, but not all, clinical needs.

Effective biomarkers are essential to early detection of alcohol use disorder (AUD) or early stages of organ damage. Early detection will make it possible for patients to consider intervention to prevent long-term medical, psychological, and social consequences of alcohol use.

Several separate, distinct diagnostic settings and circumstances are in need of reliable specific biomarkers.  Alcohol biomarkers that address the following are needed:

  • Biomarkers that detect cumulative intake of alcohol over a period of months or more; thus, a biomarker that is stable over months, reflecting duration and amount of alcohol exposure.
  • Biomarkers that detect failure of compliance after withdrawal; thus, a biomarker with a short half-life.
  • Biomarker signatures of alcohol-induced organ damage, which are likely to be organ-specific.
  • Biomarker signatures of familial risk factors for AUD.  Early identification of subjects predisposed to AUD will allow for early intervention, possible prevention, and allow the subjects to make informed personal decisions.

Characteristics of useful biomarkers are:

  • Sensitivity, specificity, accuracy, and reliability
  • Ease of use and acceptability to patient and provider
  • Found in easily obtained specimens, such as serum or plasma, urine, saliva, or hair.
  • Validity, reproducibility, affordability, and transportability to a variety of settings, including AUD treatment centers, hospitals, primary care offices, or the workplace.

Pattern-based molecular signatures —as opposed to single component biomarkers — may be predicted to provide greater sensitivity, specificity, accuracy, and reliability than single component biomarkers.  Thus, high throughput discovery approaches using genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipomics, or glycomics are encouraged.

Also of interest:

  • Improvement of turn-around time and cost efficiency of current assays for PEth, EtS, EtG and other alcohol biomarkers.
  • Design and development of point of care devices, for use in rural or remote primary care and hospital settings.

Small business efforts for improvements at any stage in the biomarker pipeline are of interest, including discovery, validation, development, and implementation to real world settings.

For clinical questions, contact:

Raye Z. Litten, Ph.D.
Telephone: 301-443-0636
Email: Raye.Litten@nih.gov

For pre-clinical questions, contact:

Kathy Jung, PhD.
Telephone: 301-443-8744
Email: Kathy.jung@nih.gov

Alcohol Biosensors

Small business applications proposing to design and produce a wearable device to monitor blood alcohol levels in real time are sought. The device should be able to quantitate blood alcohol level, and interpret and store the data or transmit it to a smartphone or other device by wireless transmission. The device should have the ability to verify standardization at regular intervals and to indicate loss of functionality. The power source should be dependable and rechargeable. Data storage and transmission must be completely secure in order to protect the privacy of the individual. A form of subject identification would be an added benefit. The device can be removable.

The alcohol biosensor device should be unobtrusive, passive in action, appealing to the wearer, and can take the form of clothing, bracelet, jewelry, or any other format located in contact with the human body. A non-invasive technology is preferred. Novel and innovative approaches to detecting blood alcohol, rather than alcohol that has exuded across the skin, are especially encouraged.

Alcohol detection technology for personal alcohol monitoring will serve useful purposes in research, clinical and treatment settings; will play a role in public safety; and will be of interest to individuals interested in keeping track of personal health parameters. 

This topic also includes the opportunity to develop appropriate data analysis systems for individual level evaluation as well as for assessment of trends in research populations.

Kathy Jung, PhD.
Telephone: 301-443-8744
Email: Kathy.jung@nih.gov

Alcohol Use and HIV Infection, and HIV Co-infection with HCV, HBV, or TB

Alcohol consumption is widely recognized as a co-factor in the sexual transmission, susceptibility to infection, and progression of infectious diseases, including HIV and HIV co-infection with HCV, HBV, or TB. However, detailed relationships between alcohol use and viral infections, disease progression, anti-viral (or anti-TB) therapy and adverse outcomes, notably in liver disease progression, are less recognized or understood particularly across different racial and ethnic groups. Recent research indicates that inflammatory pathways predominate in liver disease including alcoholic hepatitis whereas adaptive immunity plays a primary role in viral hepatitis, offering multiple targets for novel preventive and therapeutic interventions. Comprehensive studies to improve understanding of the factors underlying alcohol and viral etiologies in liver disease and the impact of anti-viral drugs on liver disease progression are needed. A better understanding of alcohol’s effects on liver disease in patients with HIV and co-infections may improve diagnosis and treatment outcomes. NIAAA supports research leading to improved diagnosis and treatment of alcohol-induced disorders in people infected with HIV, and HIV co-infection with HCV, HBV, or TB including but not limited to racial, ethnic and gender identity minorities.

Areas that may be of interest to small businesses include, but are not limited to:

  • New preventive and therapeutic approaches designed to protect the liver from alcohol and antiretroviral drug-induced liver injury in patients infected with HIV, and HIV co-infection with HCV, HBV, or TB
  • Development of therapies aimed at molecular targets that play a role in the development of alcohol-associated and viral liver and/or lung diseases.
  • Development and evaluation of drugs that mitigate the effects of oxidative stress on mitochondrial function thereby preventing liver disease progression.
  • Development of biomarkers for individuals who are most prone to alcohol-induced damage in those patients with HIV alone or HIV co-infection.

For basic research questions on alcohol and HIV, and HIV co-infection, contact:

H. Joe Wang, Ph.D.
Telephone: 301-451-0747
Email: Joe.wang1@nih.gov

For clinical or epidemiological questions on HIV, contact:

Kendall J. Bryant, Ph.D.
Telephone: 301-402-9389
Email: Kendall.Bryant@nih.gov

Electronic Diagnostic Clinical Assessment of Frailty among HIV+ Individuals with Past and/or Current Alcohol Use Disorder: Severity and Patterns

Innovative self-report, biological, and/or common clinical measures for the identification and diagnosis of frailty related to alcohol use among alcohol-using HIV patients and those with related comorbidities are sought. Measurement of frailty should be calibrated for severity of alcohol use and be both clinically useful and predictive of morbidity and mortality. Applications proposing the development of medical decision-making algorithms to inform clinical care of HIV+ individuals who drink and include frailty index(es) through an internet site are sought. The primary goal of this site will be to provide normative and educational information for providers and patients related to medical care to reduce frailty index(es) related to morbidity and mortality as primarily a useful tool for clinicians who encounter HIV patients who continue to drink and may or may not be compliant with antiretroviral treatment for suppression of viral replication and restoration of immune function.

  • Development of this site should be tested in the widest range of individuals, including but not limited to racial, ethnic and gender identity minorities, at various trajectories of progression of HIV disease and patterns of alcohol use. In particular, information from measures should be able to accurately identify individuals who are “sick quitters” and/or have high degree of frailty due to either past and/ or current alcohol use.
  • This clinical decision-making tool should be of greatest value to diagnostic assessment and interventions within clinical settings and may include the development of audio, visual, and/or training modules to support the use of appropriate diagnostic index(es) across linguistic groups.
  • Support of an electronic internet site for scoring and collection of information on HIV disease characteristics, frailty and patterns of alcohol use in clinical populations, and to provide information on a range of options for assessment of alcohol use severity in HIV+ populations (e.g. brief assessment instruments, calendar methods, biological markers, etc.).
  • Identify current and emerging methods for behavioral and/or biological intervention to reduce alcohol use in the context of HIV and improve clinical outcomes.

Kendall J. Bryant, Ph.D.
Telephone: 301-402-0332
Email: Kendall.Bryant@nih.gov

Monitoring Alcohol Use among HIV+ Patients

Of particular importance is the measurement of patterns of alcohol use among HIV+ individuals. Wearable alcohol biosensors (see related topic) should be developed to maximize acceptability and minimize stigmatization among the widest range of users. It is expected that the most effective devices will be unobtrusive devices (perhaps wrist-worn) that assess a variety of physiological measures in addition to alcohol use and that interact with smart phone technologies for additional assessment or data management features (e.g., momentary ecological assessment) related to medication adherence for HIV and related comorbidities.

Kendall J. Bryant, Ph.D.
Telephone: 301-402-0332
Email: Kendall.Bryant@nih.gov

Stem Cell Research for Alcohol-Induced Disorders

Recent advances in stem cell research provide opportunities to enhance understanding of alcohol-related conditions, including alcohol use disorder (AUD), and to develop novel medications for these conditions. The NIAAA encourages SBIR/STTR research on the use of stem cells in elucidating the pathophysiology of alcohol-related conditions and identifying novel targets for treatment.  Areas that may be of interest to small businesses include, but are not limited to:

  • Generate and disseminate induced pluripotent stem cells (iPS) from adult human cells to resemble diverse individual variations in alcohol metabolism. Use these genetic variant models to study AUD and pharmacotherapy development. Examples of these genetic variations include alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 isozyme CYP2E1, and glutathione S-transferase (GST).
  • Generate and disseminate disease-specific iPS cell lines for studies on the biology and signaling
    pathways that contribute to alcohol-related disease pathology.
  • Models derived from human iPS cells to study biological and pathological effects of alcohol and its metabolites in vivo
  • Using CRISPR (clustered regularly interspaced short palindromic repeats) gene editing technology on iPS cells to study alcohol-related disease

Peter Gao, M.D.
Telephone: 301-443-6106
Email: Peter.Gao@nih.gov

Role of Non-coding RNAs in the Neuroadaptation to Alcohol Use Disorder

Gene expression changes after alcohol exposure are well documented.  In particular, a vast network of expression changes is found in the brain (and other tissues) following both acute and chronic alcohol exposure. These neuroadaptations are thought to underlie alcohol tolerance and alcohol and alcohol use disorder as well as mediating the toxic effects of alcohol on neurodevelopment. The discovery of gene expression regulation mediated by RNA molecules that are transcribed from DNA, but do not code for protein, has set into motion a revolution in molecular biology. These novel RNAs are classified broadly as non-coding RNAs (ncRNAs) and include both small (microRNAs or miRNAs) and large classes (long non-coding RNAs or lncRNAs) that function to alter the expression of genes to which they bind and modify chromatin states. Because it is estimated that the majority of the genome consists of non-protein coding regions, of which ncRNAs make up a substantial portion, understanding how alcohol alters the expression of ncRNAs and their targets has significant potential for understanding the mechanisms of alcohol neuroadaptation. However, because of their diverse role in cellular functions and combinatorial mechanisms of action, many challenges still exist in gaining a full appreciation of the role of ncRNAs in alcohol neuroadaptation.

NIAAA seeks the development of novel technologies to both measure and interpret ncRNA gene expression signatures in the brain and/or primary neuronal cultures following alcohol exposure. These technologies could include, but are not limited to: novel methods to tag and measure ncRNAs, new imagiing techniques to monitor changes in ncRNAs, and novel bioinformatic algorithms to interpret alcohol-induced alterations in ncRNAs and predict and validate target genes.

Hemin Chin, Ph.D.           
Telephone: 301-443-1282
Email: Hemin.Chin@nih.gov

In vivo Detection of Neuromodulators in Behaving Animals

Neuromodulators, such as neuroimmune factors, modulate a wide range of brain functions and play an important role in neurodevelopment and synaptic function. To understand how activities of neuromodulators contribute to alcohol use disorders and how changes at the molecular level link to behavior, effective tools are needed to detect changes of neuromodulators in real time in the brain of behaving animals. Currently available methods that measure neuromodulator levels in the CSF fluid would not allow the analysis of dynamic changes of neuromodulators with spatial and temporal precision. To facilitate the understanding of how neuromodulators shape neuronal activity and contribute to alcohol use disorders, more accurate methods of detection are needed.

Recent advances in a variety of in vivo neurotechniques provide a great opportunity to achieve this goal. For example, cell-based fluorescent reporters, which detect the activity of G protein-coupled receptors through a fluorescent Ca2+ sensor, can be developed to detect neuromodulators that activate G protein-coupled receptors, such as chemokines. In addition, in vivo fluorescence imaging using target-activated small-molecule fluorochromes coupled with nanotechnology may also provide a powerful tool to visualize neuromodulator changes in the intact brain. 

With this SBIR/STTR solicitation, NIAAA seeks the development and application of techniques that can detect neuromodulator changes in real time with spatial and temporal precision in behaving animals.  Techniques that allow the in vivo detection of neuromodulators over an extended time period, such as implantable cell- or probe-based biosensors, will be particularly encouraged.

Changhai Cui, Ph.D.
Telephone: 301-443-1678
Email: Changhai.Cui@nih.gov

Ex vivo Screens to Identify Pharmacotherapies for Alcohol Use Disorder

High throughput screening efforts have identified many small molecules acting at biological targets thought to be important modulators of excessive alcohol drinking and other alcohol use disorder (AUD) phenotypes. Concurrently, in vivo animal models of alcohol drinking and related behavioral measures are currently used to assess potential therapeutic efficacy of medications under development. Ex vivo efficacy screens are an important link between these two activities. In contrast to many behavioral models, ex vivo tissue- and cell-based assays are desirable for their simplicity, speed, and capacity to test small drug quantities. To date, little attention has been devoted toward developing and validating neuronal tissue- and cell-based screening platforms that can be used to inform go/no go decisions for subsequent in vivo preclinical efficacy testing.

With this SBIR/STTR grant solicitation, NIAAA seeks the development and validation of ex vivo screens capable of predicting efficacy test results in preclinical behavioral models of AUD. Such assays should include array of parameters that model aspect/aspects of AUD. They should also be able to discriminate positive and negative control drugs found in the AUD pharmacotherapy literature and be sensitive to drugs with diverse mechanisms of action. In addition, the assays developed under this solicitation should be relatively rapid, simple and capable of generate readily reproducible results.

Qi-Ying Liu, M.D., M.Sci.
Telephone: 301-443-2678
Email: liuqiy@mail.nih.gov

Develop Network Pharmacology Strategy for Preclinical Medication Development

The frequent failure of using highly selective drugs for disease treatment has challenged the concept of “one gene, one drug and one disease” and led to the emergence of a new paradigm, network pharmacology, as a drug development and treatment strategy. This strategy combines the knowledge of biological networks with multiple drug targets to simultaneously regulate multiple pathways perturbed by disease conditions. Given the multi-target nature of alcohol action, alcohol use disorder (AUD) arises from brain network perturbation. The network pharmacology/combined pharmacological approach, either using drug combinations or multi-target drugs, may serve as an effective strategy for the treatment of alcohol-induced brain dysfunction and behavior disorders.

NIAAA seeks preclinical development of combined pharmacological approaches to synergistically regulate multiple drug targets for AUD. Areas that may be of interest to small businesses include, but are not limited to:

Objective 1: Develop and validate new target combinations using cellular and animal models.

Objective 2: Prioritize multi-drug targets and identify the effective drug combinations or multi-target drugs for the medication development.

Objective 3: Use high-throughput screening of compound libraries to identify multi-target drugs.

Objective 4: Encourage adaption of low throughput assays to high throughput screening, development of lead compounds, and identification of drug candidate(s) with proper pharmaceutical properties for medication development.

Changhai Cui, Ph.D.
Telephone: 301-443-1678
Email: Changhai.Cui@nih.gov

Novel Tools and Technologies to Detect the Effects of Alcohol on the CNS Structure and Activities

Alcohol affects virtually all of the major neurotransmission systems in the brain by interacting with membrane ion channels, neurotransmitter release machineries and receptors, signal transduction pathways, genes and epigenetic factors. In order to better understand the acute and chronic effects of alcohol and mechanisms of alcohol intoxication and alcohol use disorder, it is important to be able to simultaneously detect the structure and activities of large numbers of neurons with intact connections to facilitate the analysis of neurocircuits. Equally important, structure and activities in different subcellular domains (soma, dendrites, spines, axon, etc.) of CNS neurons need to be monitored with high temporal resolution. Additionally, recent developments indicate that glial cells play more important roles in the normal function of the brain and may be important alcohol targets. There is a need to monitor glia-neuron interactions.

There have been great advances in recent years in chemical and optogenetic methodologies, enabling improved ability to monitor CNS structure and activities in larger numbers and at much higher spatial and temporal resolution. Building upon these advances, NIAAA seeks SBIR/STTR research to develop the novel tools and technologies to detect the effects of alcohol on activities of specific cell types, neuron-glia interactions, and the structure and activities of large numbers of neurons in alcohol-drinking/exposure settings, preferentially with intact neural network. These include, but are not limited to, the following:

  • Improving chemical or genetic sensors to detect dynamic changes in calcium, voltage, cAMP etc.
  • Developing tools and sensors to monitor structure and activities of neurons and glial cells, and their interactions
  • Developing tools and sensors to monitor synaptic activities
  • Defining cell types in the neurocircuits
  • Developing miniature and nanoscale apparatus and sensors, or miniaturizing and optimizing detection apparatus for the study of alcohol effects
  • Developing computational methods for the acquisition and analysis of large scale data

Qi-Ying Liu, M.D., M.Sci.
Telephone: 301-443-2678
Email: liuqiy@mail.nih.gov

Changhai Cui, Ph.D.
Telephone: 301-443-1678
Email: changhai.cui@nih.gov

Research Tools

The NIAAA supports the development of new or improved tools to enhance the ability to conduct alcohol-related laboratory studies on humans and animals and to more effectively analyze data from large databases. Areas that may be of interest to small businesses include, but are not limited to:

  1. Development of novel animal models, including transgenic animals, possessing specific traits of significance for the study of alcohol use disorder (AUD), or for the study of specific pathologic disease states which arise from excessive alcohol consumption.
  2. Development of a hepatocyte cell line capable of maintaining viability and metabolic functions in culture systems for an indefinite period.
  3. Development of specialized cell culture chambers to provide controlled administration of ethanol to in vitro cell systems.
  4. Development of experimental systems that mimic organ function, including, but not limited to, co-culture and novel approaches to three dimensional culture.
  5. Development of new methods of ethanol administration to animals that produce precise dose control or that closely mimic types of alcohol exposure occurring in humans, including, but not limited to, binge drinking, acute consumption, moderate consumption and chronic consumption.
  6. Development of ligands which will enhance the potential usefulness of PET and SPECT neuroimaging technologies for the study of the etiology of AUD and related brain pathology.
  7. Development of computational, statistical or bioinformatics tools to organize and manage high throughput data obtained by genomic, functional genomic or other ‘omic strategies.
  8. Development of databases, methods for integration of databases, or data analysis systems for alcohol research.

Kathy Jung, Ph.D.
Telephone: 301-443-8744
Email: Kathy.Jung@nih.gov

Data science tools for integrating alcohol research

NIAAA-supported studies in genomics, imaging, electrophysiology and optogenetics, electronic health records, and personal wearable devices presents new challenges in analyses and interpretations and opportunities for discovery. Starting with applications submitted in 2019, all human subject data from NIAAA supported funding is expected to be deposited in publicly accessible archives. This influx of new data, along with publicly available databases and future results, can be analyzed using data science approaches. However, many of the tools needed to answer questions in alcohol research require specific applications, algorithms or toolkits that are not currently available. Data science includes and extends beyond bioinformatics and computational neuroscience to discover new relationships and pathways for complex systems of normal human function and during adaptations due to disorders or disease.

The goal is to develop data science analysis algorithms, mathematical models, and software tools in alcohol research, integrating data across disciplines and clinical and basic sciences realms.

NIAAA seeks

  • New algorithms for integrative analysis of current NIAAA and public ‘big data’ sets, including machine learning, deep learning, artificial intelligence, data mining and other model based and model-free approaches.
  • Software applications for data interfaces for aggregation, imputation, harmonization, or visualization of data from multiple sources, including current and future NIH data systems (i.e. NCBI (National Center for Biotechnology Information), dbGaP (database of Genotypes and Phenotypes), National Institute of Mental Health Data Archive), or other studies of alcohol research.
  • Algorithms and/or software tools for improving data collection, i.e. smart phone apps, extraction of specific alcohol research parameters from existing large databases and established public health studies, biological sensors or wearable devices.
  • Generation and validation of computational and/or systems biology models of alcohol exposure and use on cellular, organ, network, or organism scales.  Multiscale models are appropriate, along with models that include data from clinical and basic science research and longitudinal perspectives from initial alcohol exposure and extending though abuse, treatment, recovery and relapse.

Activities and deliverables are expected to use currently available data sets and databases. The generation of new primary data is not supported by this topic.

Elizabeth Powell, PhD
Telephone: 301-443-0786
Email: elizabeth.powell3@nih.gov

Development of novel tools to measure potentially toxic alcohol metabolites and advanced glycation end products in body fluids & other organs

Chronic and binge alcohol intake can cause multiple negative effects on many organs, including the brain, leading to changes in behavior and executive functions. Neuronal dysfunction and brain damage are frequently observed in alcoholics and the lack of objective tools for early detection of alcohol use disorders (AUD) and subsequently the long-time lag, usually in years, between the neurotoxic alcohol exposure and the clinical diagnosis of AUD with mental dysfunction need to be improved. The roles of acetaldehyde (AA), one of the main metabolites of alcohol, in alcohol-induced neurotoxicity in the brain are poorly understood. However, it is known that AA does not cross the blood brain barrier and AA produced in the brain seems to be important in causing neurotoxicity. After prolonged consumption of alcohol, if AA concentration increases in brain, it could potentially react with many cellular proteins and nucleophilic biomolecules to covalent AA-protein or DNA adducts. In addition, early glycation products resulting from excessive alcohol intake, or elevated amounts of glucose or fructose can undergo progressive modifications over time to generate irreversible cross-linked products, called advanced glycation end products (AGEs). AGEs usually alter the functions target proteins and thereby change their physical and properties. Consequently, accumulation of AGEs that have been implicated in the development of many of the pathological sequelae including neurodegenerative diseases such as Alzheimer disease, Parkinson disease, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis. Therefore, development of novel techniques to measure potentially toxic alcohol metabolites and its adducts and/ or AGEs would be important early detection of AUD. In this connection, areas of interest include, but are not limited to:

  • Develop tools/kits for early detection and to measure AA-adducts and AGEs in serum, CSF, brain and other organs of AUDs in animal models and in pre-clinical settings and their relationship to the biomarkers of neuro-inflammation.
  • Develop tools/kits to measure AA-adducts and AGEs, like other oxidative and carbonyl stress end products; advanced lipoperoxidation end products (ALE) and advanced oxidation protein products (AOPP).
  • Develop tools to study interaction of AA-adducts and AGEs with RAGE (Receptor for AGEs) and measurement of structural damage to the extracellular matrix and other components.
  • Measure AGE–RAGE mediated activation of nuclear factor NF-B, cytokines and growth factors genes and increased expression of neuro-inflammatory molecules.

Mohammed Akbar, Ph.D.
Telephone: 301-443-6009
Email: akbarm@mail.nih.gov

Single Cell Genomics (RNA Sequencing): Application to Develop Molecular Markers of Alcohol Use Disorder

Due to advancements in DNA biotechnology, single cell genomics (RNA Sequencing (RNA-Seq)) has become an attractive technique to conduct systematic and unbiased discovery of gene expression profiles. The RNA-Seq approach will reveal the molecular fingerprint of cell states and their predicted signaling circuits in tissues across development and disease.  The objective of this SBIR concept is to measure RNA-Seq of human blood cells to identify gene profiles and use them as biomarkers to monitor different stages of alcohol use disorders.

Some examples of the topics could be to: 

  • Develop rapid and cost-effective RNA seq methods/technologies in human blood cells
  • Characterize the gene expression profile in human blood cells of AUD subjects. 
  • Identify and validate specific gene profile signature as biomarkers in AUD subjects.
  • Develop technology/device for rapid screening different stages of alcohol use and AUD

Abbas Parsian, Ph.D.
Telephone: 301-443-5733
E-mail: parsiana@nih.gov

NIAAA Clinical Trials Topics

Medications Development

Pharmacotherapy offers a promising means for treating AUD. Currently, there are four Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of AUD: disulfiram (Antabuse®), oral naltrexone (Revia®), acamprosate (Campral®), and the injectable suspension formulation of naltrexone (Vivitrol®). Another medication, nalmefene (Selincro®), has recently been approved by the European Medicines Agency (EMA). However, given the heterogeneous nature of AUD, many patients have limited or no response to the aforementioned medications. Because of this, developing and evaluating new, more efficacious medications remains a high priority.

During the past five decades, alcohol research has enriched our understanding of the biological mechanisms underlying AUD. Various neurotransmitter systems, neuromodulators, and intracellular signaling pathways have a role in AUD. To date, more than 35 promising targets have been shown to alter alcohol drinking behavior. Some of the new promising targets include, but are not limited to, corticotrophin-releasing factor1 (CRF-1), adrenergic α1 and α2, vasopressin 1B, orexin 1 and 2, opioid receptor-like (NOP), opioid kappa, 5-HT2, GABA-A and GABA-B, metabotropic glutamate (mGluR), glutamate transporter (GLT), nicotinic acetylcholine (nAChR), phospodiesterase (PDE), glial derived neurotrophic factor (GDNF), and neuroimmune and epigenetic modulators. New medications that bind to these and additional targets are needed.

Candidate medications may include novel and re-purposed compounds. However, grant applications that propose to study compounds already extensively investigated or currently being studied patients with AUD will not be accepted. Thus, applications proposing the use of naltrexone, acamprosate, disulfiram, topiramate, ondansetron, varenicline, gabapentin, and baclofen are not responsive to this topic.

Specific areas of interest include medications that target one or more domains of the addiction cycle, including reward, stress and negative affect, incentive salience, executive function, habituation, and impulsivity/compulsivity.

For questions, contact:

Raye Z. Litten, Ph.D.
Telephone: 301-443-0636
Email: Raye.Litten@nih.gov

Additional targets for pharmaceutical development include, but are not limited to agents that attenuate excessive alcohol use and other symptoms of AUD, e.g., craving, sleep problems, and negative affect as well as those that hold promise for the treatment of alcoholic hepatitis, liver fibrosis, cirrhosis, pancreatitis, cardiomyopathy, or other alcohol-induced tissue damage.
For pre-clinical questions, contact:

Mark Egli, Ph.D. (Neuroscience and behavior)
Telephone: 301-594-6382
Email: Mark.Egli@nih.gov

Svetlana Radaeva, Ph.D. (Organ damage)
Telephone: 301-433-1189
Email: Svetlana.Radaeva@nih.gov

Technological Methods for the Treatment of Hazardous Drinking and Alcohol Use Disorder

  • Develop, improve, and validate ecological momentary assessment (EMA) methods for capturing real-time data for use in alcohol clinical trials and treatment paradigms.
  • Use technology (e.g. EMA, brain imaging) and innovative statistical methods (e.g., machine learning, systems science dynamic models) appropriate for analysis of “big data” (i.e., time intensive, multisource data) to inform our understanding of mechanisms underlying the initiation, maintenance, and recovery from problematic drinking in both treatment and naturalistic settings. Leverage unique features of mobile technologies to provide personalized monitoring and just-in-time interventions including but not limited to a variety of racial/ethnic and linguistic populations.
  • Optimize existing technologies to increase their utilization and effectiveness in specific treatment contexts (e.g., primary care) and improve patient-provider communication to decrease harmful drinking including across racial, ethnic and linguistic groups.
  • Develop and test computerized versions of empirically-supported treatments, including but not limited to in languages other than English.
  • Develop and test novel computerized interventions which capitalize on hypothesized brain-based or behavioral mechanisms underlying drinking
  • Develop software to train potential treatment professionals on how to provide evidence-based treatments
  • Devise novel methods (e.g., Web-mining software of social networking sites) that capture social network information among groups at risk for alcohol use disorder and high-risk drinking, including but not limited to racial and ethnic minority populations.
  • Develop and test the efficacy of neurophysiological treatment approaches such as transcranial magnetic stimulation, neurofeedback, and deep brain stimulation.

Anita Bechtholt, Ph.D.
Telephone: 301-443-9334
Email: anita.bechtholt@nih.gov

Prevention

This area of interest focuses on the development and evaluation of innovative prevention and intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Applicants are strongly encouraged to consult with research methodologists and statisticians to ensure that state-of-the-art approaches to design, analysis, and interpretation of studies under this topic are used. Areas that may be of interest to small businesses include, but are not limited to:

  • Development and evaluation of innovative prevention/intervention programs, or specific materials for integration into existing programs, which utilize state-of-the-art technology and are based on currently accepted clinical and behavioral strategies. Special emphasis should be placed on the needs of high-risk groups, ethnic and minority populations, youth, children of individuals with alcohol use disorder, women, the handicapped, sexual and gender minority populations, and the elderly. Examples of such materials include school-based curricula, interactive videos, computer-based multimedia programs, training manuals for teachers or parents, and community-based programs.
  • Development and evaluation of educational materials designed to intervene with the elderly around specific age-related risks for alcohol problems. Particular attention should be given to age-related reductions in alcohol tolerance, interactions between alcohol and prescription and over-the-counter medications, possible exacerbation of some medical conditions common among the elderly, potential biomedical and behavioral consequences of excessive alcohol use, and the role of alcohol in falls, fires, burns, pedestrian and traffic injuries, and other unintentional injuries.
  • Development and evaluation of statistical analysis programs tailored to the design and analysis of alcohol prevention-relevant research. Programs could focus on a variety of areas including: imputation of missing data under varying design assumptions; development and application of statistical models suited to small sample sizes common in racial and ethnic minority research; simulation of distributions of outcomes based on varying mixtures of sample populations; application of chronic or infectious disease models to targeted communities; and models of the potential effect of various policy-based interventions, such as increased taxation or reduction of outlet density by license revocation and control.

Robert C. Freeman, Ph.D.
Telephone: 301-443-8820
Email: Robert.Freeman@nih.gov

Improving the Delivery of Alcohol Treatment Services

NIAAA’s treatment services research program studies the organization, management, and financing of alcohol treatment services, and how these affect service availability, access, utilization, cost, and quality. Needed innovations in this area include the development of state-of-the-art technologies, software, and protocols to expand and improve the delivery of evidence-based treatment for alcohol use disorders.

Areas that may be of interest to small businesses include, but are not limited to, the development and assessment of software or tools to:

  • assist clinicians in selecting and delivering evidence-based treatments consistent with patient needs and available staff and program resources across racially, ethnically and linguistically diverse populations. Special attention should be paid to promoting fidelity of treatment delivery in real-world contexts. For example: software to enable the creation or use of clinical decision support systems, screening protocols, or patient registries; prescription medication management tools; scripts or guides for delivery of brief interventions; and interactive training resources.
  • support long-term recovery, by facilitating patients’ continued engagement in recovery support services as an adjunct to or after treatment. For example: software to assist patients in self-management and self-monitoring of drinking behaviors, cues, or triggers, and/or in locating treatment resources or recovery support services.
  • assist treatment programs and service agencies in measuring clinically relevant performance indicators or improvements in quality of service provision.
  • promote engagement and mitigate burnout among counselors and others engaged in direct treatment service delivery. Tools are needed to reinforce training on therapeutic techniques; provide minimally-obtrusive methods for monitoring and enhancing fidelity of service delivery; engage counselors in mindfulness or other strategies to manage job stress and reduce burnout; and provide front-line counselors with supports essential to maintaining productive therapeutic relationships with patients.

Laura Kwako, Ph.D.
Telephone: 301-451- 8507
Email: Laura.kwako@nih.gov

Fetal Alcohol Spectrum Disorder (FASD) and Alcohol-Related Birth Defects

FASD is the collective term for the broad array of adverse effects resulting from in utero alcohol exposure. Fetal Alcohol Syndrome (FAS), the first form of FASD discovered and most well-known, is characterized by craniofacial abnormalities, growth retardation, and nervous system impairments that often include mental retardation. Other diagnostic categories include partial FAS, alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). Children and adults with FASD may exhibit multiple cognitive, behavioral, and emotional deficits that impair daily functioning in many domains. The NIAAA supports research leading to improved diagnosis and assessment of prenatal exposure, impairment and disability, as well as the development of therapeutic interventions, including tools to enhance academic and daily living skills across diverse racial, ethnic and linguistic populations. Areas that may be of interest to small businesses include, but are not limited to:

  • Development and assessment of diagnostic and/or screening methods, tools, or technologies to improve earlier identification of fetuses and/or children affected by prenatal alcohol exposure.
  • Development and validation of biomarkers that can be used to verify prenatal alcohol exposure in neonates or predict those individuals with neurobehavioral deficits later in life.
  • Development and validation of assessment methods to provide more accurate clinical diagnosis of FASD at all life stages.
  • Development and testing of skill-building, therapeutic, and education program products that enhance the social, cognitive, adaptive and motor abilities of individuals with FASD.
  • Development of neurobehavioral tools or instruments to assess responsiveness of individuals with FASD to medications and/or cognitive/behavioral therapies.
  • Development of accurate measures of the responsiveness of children affected by prenatal exposure to alcohol to stress and predictors of vulnerability to alcohol-drinking or other psychopathology during adolescence and adulthood.
  • Development and evaluation of educational and training programs designed to enhance the skills of non-professional caregivers in dealing with the problems associated with FAS.
  • Development and validation of innovative methods, tools or technology to prevent harmful drinking during pregnancy.

For basic research questions, contact:

William Dunty, Ph.D.
Telephone: 301-443-7351
Email: William.Dunty@nih.gov

For prevention research questions, contact:

I-Jen Castle, Ph.D.
Telephone: 301-827-4406
Email: i-jen.castle@nih.gov

Deidra Roach
Telephone: 301-443-5820
Email: Deidra.Roach@nih.gov

Development of Clinical Biomarkers of Alcohol Exposure and Alcohol-Induced Organ Damage

There is a well-recognized need for prognostic and diagnostic biomarkers of alcohol exposure, for biomarkers of the response to clinical treatment, and for biomarkers to monitor abstinence in high-risk individuals. Quantitative and qualitative markers of high-risk drinking behavior and alcohol-induced tissue damage would greatly improve medical efforts to recognize and treat alcohol-related disorders. Currently, no clinically available laboratory test can reliably diagnose duration of alcohol use or predict the progression of alcohol-induced organ damage. Traditional alcohol biomarkers fail to provide long-term information. More recently developed alcohol biomarkers (ethanol metabolites phosphatidylethanol (PEth), ethyl glucuronide (EtG) and ethyl sulfate (EtS)) display improved sensitivity, specificity, and accuracy over classical biomarkers. Their useful range of a few days (EtG) to 2-4 weeks (PEth) addresses many, but not all, clinical needs.

Effective biomarkers are essential to early detection of alcohol use disorder (AUD) or early stages of organ damage. Early detection will make it possible for patients to consider intervention to prevent long-term medical, psychological, and social consequences of alcohol use.

Several separate, distinct diagnostic settings and circumstances are in need of reliable specific biomarkers.  Alcohol biomarkers that address the following are needed:

  • Biomarkers that detect cumulative intake of alcohol over a period of months or more; thus a biomarker that is stable over months, reflecting duration and amount of alcohol exposure.
  • Biomarkers that detect failure of compliance after withdrawal; thus a biomarker with a short half-life.
  • Biomarker signatures of alcohol-induced organ damage, which are likely to be organ-specific.
  • Biomarker signatures of familial risk factors for AUD.  Early identification of subjects predisposed to AUD will allow for early intervention, possible prevention, and allow the subjects to make informed personal decisions.
     

Characteristics of useful biomarkers are:

  • Sensitivity, specificity, accuracy, and reliability
  • Ease of use and acceptability to patient and provider
  • Found in easily obtained specimens, such as serum or plasma, urine, saliva, or hair.
  • Validity, reproducibility, affordability, and transportability to a variety of settings, including AUD treatment centers, hospitals, primary care offices, or the workplace.

Pattern-based molecular signatures —as opposed to single component biomarkers --may be predicted to provide greater sensitivity, specificity, accuracy, and reliability than single component biomarkers.  Thus, high throughput discovery approaches using genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipomics, or glycomics are encouraged.

Also of interest:

  • Improvement of turn-around time and cost efficiency of current assays for PEth, EtS, EtG and other alcohol biomarkers
  • Design and development of point of care devices, for use in rural or remote primary care and hospital settings.

Small business efforts for improvements at any stage in the biomarker pipeline are of interest, including discovery, validation, development, and implementation to real world settings.

For clinical questions, contact:

Raye Z. Litten, Ph.D.
Telephone: 301-443-0636
Email: Raye.Litten@nih.gov

For pre-clinical questions, contact:
Kathy Jung, PhD.
Telephone: 301-443-8744
Email: Kathy.jung@nih.gov

Alcohol Biosensors

Small business applications proposing to design and produce a wearable device to monitor blood alcohol levels in real time are sought. The device should be able to quantitate blood alcohol level, and interpret and store the data or transmit it to a smartphone or other device by wireless transmission. The device should have the ability to verify standardization at regular intervals and to indicate loss of functionality. The power source should be dependable and rechargeable. Data storage and transmission must be completely secure in order to protect the privacy of the individual. A form of subject identification would be an added benefit. The device can be removable.

The alcohol biosensor device should be unobtrusive, passive in action, appealing to the wearer, and can take the form of clothing, bracelet, jewelry, or any other format located in contact with the human body. A non-invasive technology is preferred. Novel and innovative approaches to detecting blood alcohol, rather than alcohol that has exuded across the skin, are especially encouraged.

Alcohol detection technology for personal alcohol monitoring will serve useful purposes in research, clinical and treatment settings; will play a role in public safety; and will be of interest to individuals interested in keeping track of personal health parameters. 

This topic also includes the opportunity to develop appropriate data analysis systems for individual level evaluation as well as for assessment of trends in research populations.

Kathy Jung, PhD.
Telephone: 301-443-8744
Email: Kathy.jung@nih.gov

Alcohol Use and HIV Infection, and HIV Co-infection with HCV, HBV, or TB

Alcohol consumption is widely recognized as a co-factor in the sexual transmission, susceptibility to infection, and progression of infectious diseases, including HIV and HIV co-infection with HCV, HBV, or TB. However, detailed relationships between alcohol use and viral infections, disease progression, anti-viral (or anti-TB) therapy and adverse outcomes, notably in liver disease progression, are less recognized or understood particularly across different racial and ethnic groups. Recent research indicates that inflammatory pathways predominate in liver disease including alcoholic hepatitis whereas adaptive immunity plays a primary role in viral hepatitis, offering multiple targets for novel preventive and therapeutic interventions. Comprehensive studies to improve understanding of the factors underlying alcohol and viral etiologies in liver disease and the impact of anti-viral drugs on liver disease progression are needed. A better understanding of alcohol’s effects on liver disease in patients with HIV and co-infections may improve diagnosis and treatment outcomes. NIAAA supports research leading to improved diagnosis and treatment of alcohol-induced disorders in people infected with HIV, and HIV co-infection with HCV, HBV, or TB including but not limited to racial, ethnic and gender identity minorities.

Areas that may be of interest to small businesses include, but are not limited to:

  • New preventive and therapeutic approaches designed to protect the liver from alcohol and antiretroviral drug-induced liver injury in patients infected with HIV, and HIV co-infection with HCV, HBV, or TB
  • Development of therapies aimed at molecular targets that play a role in the development of alcohol-associated and viral liver and/or lung diseases.
  • Development and evaluation of drugs that mitigate the effects of oxidative stress on mitochondrial function thereby preventing liver disease progression.
  • Development of biomarkers for individuals who are most prone to alcohol-induced damage in those patients with HIV alone or HIV co-infection. 

For basic research questions on alcohol and HIV, and HIV co-infection, contact:

H. Joe Wang, Ph.D.
Telephone: 301-451-0747
Email: Joe.wang1@nih.gov

For clinical or epidemiological questions on HIV, contact:

Kendall J. Bryant, Ph.D.
Telephone: 301-402-9389
Email: Kendall.Bryant@nih.gov

Electronic Diagnostic Clinical Assessment of Frailty among HIV+ Individuals with Past and/or Current Alcohol Use Disorder: Severity and Patterns

Innovative self-report, biological, and/or common clinical measures for the identification and diagnosis of frailty related to alcohol use among alcohol-using HIV patients and those with related comorbidities are sought. Measurement of frailty should be calibrated for severity of alcohol use and be both clinically useful and predictive of morbidity and mortality. Applications proposing the development of medical decision-making algorithms to inform clinical care of HIV+ individuals who drink and include frailty index(es) through an internet site are sought. The primary goal of this site will be to provide normative and educational information for providers and patients related to medical care to reduce frailty index(es) related to morbidity and mortality as primarily a useful tool for clinicians who encounter HIV patients who continue to drink and may or may not be compliant with antiretroviral treatment for suppression of viral replication and restoration of immune function.

  • Development of this site should be tested in the widest range of individuals, including but not limited to racial, ethnic and gender identity minorities, at various trajectories of progression of HIV disease and patterns of alcohol use. In particular, information from measures should be able to accurately identify individuals who are “sick quitters” and/or have high degree of frailty due to either past and/ or current alcohol use.
  • This clinical decision-making tool should be of greatest value to diagnostic assessment and interventions within clinical settings and may include the development of audio, visual, and/or training modules to support the use of appropriate diagnostic index(es) across linguistic groups.
  • Support of an electronic internet site for scoring and collection of information on HIV disease characteristics, frailty and patterns of alcohol use in clinical populations, and to provide information on a range of options for assessment of alcohol use severity in HIV+ populations (e.g. brief assessment instruments, calendar methods, biological markers, etc.).
  • Identify current and emerging methods for behavioral and/or biological intervention to reduce alcohol use in the context of HIV and improve clinical outcomes.

Kendall J. Bryant, Ph.D.
Telephone: 301-402-0332
Email: Kendall.Bryant@nih.gov

Monitoring Alcohol Use among HIV+ Patients

Of particular importance is the measurement of patterns of alcohol use among HIV+ individuals. Wearable alcohol biosensors (see related topic) should be developed to maximize acceptability and minimize stigmatization among the widest range of users. It is expected that the most effective devices will be unobtrusive devices (perhaps wrist-worn) that assess a variety of physiological measures in addition to alcohol use and that interact with smart phone technologies for additional assessment or data management features (e.g. momentary ecological assessment) related to medication adherence for HIV and related comorbidities.

Kendall J. Bryant, Ph.D.
Telephone: 301-402-0332
Email: Kendall.Bryant@nih.gov

Data science tools for integrating alcohol research

NIAAA-supported studies in genomics, imaging, electrophysiology and optogenetics, electronic health records, and personal wearable devices presents new challenges in analyses and interpretations and opportunities for discovery. Starting with applications submitted in 2019, all human subject data from NIAAA supported funding is expected to be deposited in publicly accessible archives. This influx of new data, along with publicly available databases and future results, can be analyzed using data science approaches. However, many of the tools needed to answer questions in alcohol research require specific applications, algorithms or toolkits that are not currently available. Data science includes and extends beyond bioinformatics and computational neuroscience to discover new relationships and pathways for complex systems of normal human function and during adaptations due to disorders or disease.

The goal is to develop data science analysis algorithms, mathematical models, and software tools in alcohol research, integrating data across disciplines and clinical and basic sciences realms.

NIAAA seeks

  • New algorithms for integrative analysis of current NIAAA and public ‘big data’ sets, including machine learning, deep learning, artificial intelligence, data mining and other model based and model-free approaches.
  • Software applications for data interfaces for aggregation, imputation, harmonization, or visualization of data from multiple sources, including current and future NIH data systems (i.e. NCBI (National Center for Biotechnology Information), dbGaP (database of Genotypes and Phenotypes), National Institute of Mental Health Data Archive), or other studies of alcohol research.
  • Algorithms and/or software tools for improving data collection, i.e. smart phone apps, extraction of specific alcohol research parameters from existing large databases and established public health studies, biological sensors or wearable devices.
  • Generation and validation of computational and/or systems biology models of alcohol exposure and use on cellular, organ, network, or organism scales.  Multiscale models are appropriate, along with models that include data from clinical and basic science research and longitudinal perspectives from initial alcohol exposure and extending though abuse, treatment, recovery and relapse.

Activities and deliverables are expected to use currently available data sets and databases. The generation of new primary data is not supported by this topic.

Elizabeth Powell, PhD
Telephone: 301-443-0786
Email: elizabeth.powell3@nih.gov

Development of novel tools to measure potentially toxic alcohol metabolites and advanced glycation end products in body fluids & other organs

Chronic and binge alcohol intake can cause multiple negative effects on many organs, including the brain, leading to changes in behavior and executive functions. Neuronal dysfunction and brain damage are frequently observed in alcoholics and the lack of objective tools for early detection of alcohol use disorders (AUD) and subsequently the long-time lag, usually in years, between the neurotoxic alcohol exposure and the clinical diagnosis of AUD with mental dysfunction need to be improved. The roles of acetaldehyde (AA), one of the main metabolites of alcohol, in alcohol-induced neurotoxicity in the brain are poorly understood. However, it is known that AA does not cross the blood brain barrier and AA produced in the brain seems to be important in causing neurotoxicity. After prolonged consumption of alcohol, if AA concentration increases in brain, it could potentially react with many cellular proteins and nucleophilic biomolecules to covalent AA-protein or DNA adducts. In addition, early glycation products resulting from excessive alcohol intake, or elevated amounts of glucose or fructose can undergo progressive modifications over time to generate irreversible cross-linked products, called advanced glycation end products (AGEs). AGEs usually alter the functions target proteins and thereby change their physical and properties. Consequently, accumulation of AGEs that have been implicated in the development of many of the pathological sequelae including neurodegenerative diseases such as Alzheimer disease, Parkinson disease, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis. Therefore, development of novel techniques to measure potentially toxic alcohol metabolites and its adducts and/ or AGEs would be important early detection of AUD. In this connection, areas of interest include, but are not limited to:

  • Develop tools/kits for early detection and to measure AA-adducts and AGEs in serum, CSF, brain and other organs of AUDs in animal models and in pre-clinical settings and their relationship to the biomarkers of neuro-inflammation.
  • Develop tools/kits to measure AA-adducts and AGEs, like other oxidative and carbonyl stress end products; advanced lipoperoxidation end products (ALE) and advanced oxidation protein products (AOPP).
  • Develop tools to study interaction of AA-adducts and AGEs with RAGE (Receptor for AGEs) and measurement of structural damage to the extracellular matrix and other components.
  • Measure AGE–RAGE mediated activation of nuclear factor NF-B, cytokines and growth factors genes and increased expression of neuro-inflammatory molecules.

Contact information:

Mohammed Akbar, Ph.D.
Tel: 301-443-6009
Email: akbarm@mail.nih.gov

Single Cell Genomics (RNA Sequencing): Application to Develop Molecular Markers of Alcohol Use Disorder

Due to advancements in DNA biotechnology, single cell genomics (RNA Sequencing (RNA-Seq)) has become an attractive technique to conduct systematic and unbiased discovery of gene expression profiles. The RNA-Seq approach will reveal the molecular fingerprint of cell states and their predicted signaling circuits in tissues across development and disease.  The objective of this SBIR concept is to measure RNA-Seq of human blood cells to identify gene profiles and use them as biomarkers to monitor different stages of alcohol use disorders.

Some examples of the topics could be to: 

  • Develop rapid and cost-effective RNA seq methods/technologies in human blood cells
  • Characterize the gene expression profile in human blood cells of AUD subjects. 
  • Identify and validate specific gene profile signature as biomarkers in AUD subjects.
  • Develop technology/device for rapid screening different stages of alcohol use and AUD

Abbas Parsian, Ph.D.
Telephone: 301-443-5733
E-mail: parsiana@nih.gov

Direct your general questions about the SBIR/STTR program or scientific/research issues to:

Megan Ryan, M.B.A.
National Institute on Alcohol Abuse and Alcoholism
6700B Rockledge Dr.
Rockville, MD 20852-1705

For administrative and business management questions, contact:

Mr. Jeff Thurston
Grants Management Specialist
National Institute on Alcohol Abuse and Alcoholism
Phone: 301-443-9801, Fax: 301-443-3891
Email: jeffrey.thurston@nih.gov