niaaa: current and future priorities · primary goal of coga: to find and understand genes that...

NIAAA: Current and Future Priorities

George F. Koob, Ph.D. Director

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Cost and Scope of Addiction

Alcohol Issues Across the Lifespan

•  NIAAA supports research to study how alcohol can affect health and well-being at various stages of life.

Alcohol

Prenatal Alcohol

Exposure

Binge Drinking Organ

Damage

Medication Interactions

Alcohol Dependence Alcoholic

Family Environment

Lifespan Transcending Themes •  Neurobiology •  Metabolism •  Genetics •  Epigenetics •  Epidemiology •  Health Services Research

Special Thanks to Dr. Ken Warren

Acting Director NIAAA 2008- 2014

Deputy Director NIAAA

Czar of Fetal Alcohol Syndrome Portfolio

NIAAA Extramural Grant Portfolio, FY 2013 Total Funding $319,759,079 n=955

(sequestration)

•  International Research •  Mechanisms of

Behavior Change •  Underage Drinking

Treatment (n=102)

$15,428,018

$42,571,054 $32,443,946

$31,428,670

$74,364,840

$123,522,551

Health Services (n=32)

Prevention (n=84)

Epidemiology (n=95)

Metabolism & Health Effects (n=239)

Neuroscience & Behavior (n=403)

NIAAA Trans-Divisional Research Emphasis Areas

•  Biomarkers •  Fetal Alcohol Spectrum

Disorders •  Genes and Environment

•  Health Disparities •  HIV and AIDS •  Systems Biology •  Medications Development

1. Fetal Alcohol Syndrome/ Fetal Alcohol Spectrum Disorders

2. Underage and College Drinking

3. Neurobiology of Alcoholism

4. Genetics of Alcoholism

5. Treatment of Alcoholism

6. . Alcoholic Liver Disease

7. HIV/AIDS

Current NIAAA Priority Programs

•  Improve diagnostic capabilities to determine the full prevalence of Fetal Alcohol Spectrum Disorder (FASD) and identify women and children in need of care and services

•  Improve detection of risk drinking during pregnancy by developing new biomarkers

•  Given the subtlety of FAS facial deficits – improve the acumen for FAS facial recognition through 3-D photography and computer analysis

•  Refine our understanding of the complexities in the neurobehavioral phenotype associated with FASD

•  Prevent and/or ameliorate the effects of FASD through nutritional supplementations, pharmacology, or enhanced CNS stimulation

FASD Research Research Challenges:

•  Consortium of approximately 8 Principal Investigators and many Co-investigators

•  Animal and human research

•  International project with study sites in U.S., South Africa, Europe, Asia

•  Research from CIFASD was critical to acceptance by APA of a new diagnostic category for Neurobehavioral Disorder: Prenatal Alcohol Exposed

Collaborative Initiative on Fetal Alcohol Spectrum Disorders (FASD) – ongoing since 2003 :

FASD Consortia

Prenatal Alcohol, Sudden Infant Death Syndrome (SIDS)), and Stillbirth (PASS)

•  Joint initiative with NICHD and Deafness Institute •  On-going since 2003

•  Study sites in: •  South and North Dakota – population Caucasian and American

Indian •  South Africa – mixed ancestry population known as Cape Coloured

•  Major dependent variable is alcohol, secondary tobacco and other drugs (e.g., methamphetamine); study is powered on rarest outcome, i.e., SIDS







7. HIV/AIDS


•  Complementing N-CANDA, NADIA uses animal models to assess the effects of adolescent alcohol exposure on the adult brain.

•  Unlike studies with human adolescents, animal studies can control environmental factors and administer alcohol during adolescence.

Neurobiology of Adolescent Drinking in Adulthood (NADIA) – Animal Studies

Objectives: •  Study effects of alcohol exposure on trajectory of adolescent

brain development in the context of development

•  Examine dose, duration, and timing effects of alcohol exposure

•  Determine what structural and functional anomalies are the result of alcohol exposure and what predates, and may predict, heavy alcohol use

•  Identify neuroimaging and/or neurocognitive brain markers that predict onset of AUD and other psychopathology

National Consortium on Alcohol and Neurodevelopment in Adolescence

Ken Sher (SAB)

Andrea Hussong (SAB)

Raquel Gur (SAB)

Susan Tapert Sandra Brown

Mike DeBellis

Duncan Clark Bonnie Nagel

Sites Advisors Collabora0ons

OHSU Portland

Dolf Pfefferbaum Torsten Rohlfing

Ian Colrain Fiona Baker

Duke

PiLsburgh SRI/Stanford

UC San Diego

Robert Zucker (SAB)

Supported by: NIAAA NIMH NICHD NIDA

•  In response to a request from NIAAA’s College Presidents Working Group, NIAAA engaged top researchers in the field to develop an interactive, user-friendly, print and online “decision support system” to help colleges and universities select appropriate strategies to meet their alcohol intervention goals.

•  The tool will allow college presidents and staff to review the strategies they are already using as well as explore others that may serve them better.

•  Users will be able to search for strategies according to intervention level (e.g., individual, group, campus-wide, community) and evaluate other factors, such as effectiveness, barriers and costs, affecting implementation

•  We envision that much like online shopping applications, the online tool will allow users to select a set of strategies for side-by-side comparisons

College Drinking College Drinking Intervention Matrix – Coming Soon







7. HIV/AIDS


Conceptual Framework for Neurobiological Bases of the Transition to Excessive Drinking

•  An 11 site multidisciplinary consortium devoted to identifying molecular, cellular, and behavioral neuroadaptations that occur in the brain due to alcohol exposure that contribute to excessive alcohol consumption in some individuals.

•  The current objective of INIA is to confirm previously identified gene targets and identify druggable targets that are the most promising for medications development for the treatment of alcoholism.

•  This will be achieved using: ⁻  the extensive INIA genomics data set ⁻  the INIA mutant mouse and behavioral testing cores ⁻  INIA electrophysiology expertise

Integrative Neuroscience Initiative on Alcoholism (INIA)

NeuroadaptaQon

•  A cooperative consortium of 15 Principal Investigators from 9 academic institutions across the US.

•  The INIA stress consortium uses a state-of-the art translational approach (mice, monkeys and humans) to:

Integrative Neuroscience Initiative on Alcoholism (INIA)

INIA-‐Stress

Ø  understand the interaction of genetic variation and stress on the promotion of excessive drinking Ø  identify novel, effective and tailored treatment

strategies for alcoholism.

Primary Goal of COGA: To find and understand genes that affect the risk for the development of alcoholism and related disorders. This is being accomplished through linkage, GWAS, and whole-exome sequencing studies as well as gene expression and epigenetic studies.

The COGA family pedigrees are densely affected with alcoholism containing at least 2 alcohol-dependent first-degree relatives in addition to an alcohol dependent proband.

Participants from 9 US sites

Collaborative Study on the Genetics of Alcoholism (COGA)






6. Alcoholic Liver Disease

7. HIV/AIDS


• Mission: To improve the care and treatment of those affected by AUD, high-risk drinking, and alcohol-related medical disorders by supporting the development of effective and safe medications that are accepted and used by clinicians and patients.

• Overall Goal: Translate promising medications from discovery to preclinical and human clinical testing to real-world effectiveness and implementation studies.

NIAAA Medications Development Program for Alcohol Use Disorder (AUD), High-Risk

Drinking, and Alcohol-Related Medical Disorders

SCREENING MODELS

VALIDATION PROCESS: BIDIRECTIONAL INTEGRATION

Molecular Targets

Animal Models

Human Laboratory

Models

Clinical Trials

PURPOSE

• Bridge gap between preclinical studies and expensive, time-consuming Phase 3 trial

• Quick turnaround (1½ years)

• Access to many CNS compounds of pharmaceutical companies

• Ability to deal with intellectual property

• Study design flexibility

NIAAA Clinical Investigation Group (NCIG)

Network of Sites for Proof of Concept Trials







7. HIV/AIDS


Building a New Research Program for Alcoholic Hepatitis

Create a rich and fertile

environment for new and

collaborations

Understand the pathogenesis and identify

new molecular targets

Identify best therapeutic regiments based on patients’ risk factors, pathogenesis,

prognosis

The Veterans Aging Cohort Study (VACS) is a prospective, observational cohort study of HIV- positive and an age/race/site matched control group of HIV- negative veterans in care in the United States. The study's aim is to understand the role of comorbid medical and psychiatric disease in determining clinical outcomes in HIV infection. The study has a special focus on the role of alcohol use and abuse in determining clinical outcomes.

Veterans Aging Cohort Study (VACS)

1. Functional Merge: Co-morbidity, Co- training, Co- Prevention, Co- Treatment

2. Neurobiology of Intoxication

3. Sleep and Alcoholism

4. Post traumatic Stress Disorder

5. Standardization of Prevention Options for Middle and Secondary Schools

5. Standardization of Prevention Options for College Campuses

Future NIAAA Priority Programs

Collaborative Research on Addiction at NIH (CRAN)

Uber CRAN? National Longitudinal Study of Neurodevelopmental

Consequences of Substance Use

Study Aims: What is the impact of the sporadic versus the regular use of marijuana, alcohol, nicotine and other substances on the developing brain? What are the neurodevelopmental pathways that link adolescent substance use and pre-existing or emerging mental illnesses? What are the effects of multiple substances in combination? Partnering Agencies: The study will be led by the Collaborative Research on Addiction (CRAN) at NIH (National Institute on Drug Abuse [NIDA], National Institute on Alcohol Abuse and Alcoholism [NIAAA], and the National Cancer Institute [NCI]) in collaboration with the National Institute of Child Health and Human Development (NICHD) and potentially other Institutes (National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH)). We are also seeking partnership with other agencies (CDC, FDA, ONDCP) Study Design: The study will consist of a large representative cohort (i.e. approximately 10,000) youth that will be followed over a 10-year period, beginning before drug use is initiated and continuing into early adulthood.

1. FDA approval for medications for treatment of alcoholism

2. Implementation of effective behavioral treatments for alcoholism

3. Implementation of effective prevention strategies for adolescent drinking

4. Implementation of effective prevention strategies for drinking during pregnancy

5. Elimination of alcohol –related HIV pathology

6. Establishment of effective treatments for fetal alcohol spectrum disorder (FASD)

7. Development effective treatments for alcoholic liver disease

8. Appropriate treatment of co-morbidities associated with alcoholism

9. Successful recruitment of young investigators to the alcohol field, elimination of disparities in the alcohol field. Equal pay for women and minorities in the alcohol field

Where we want to be

Thank You! George F. Koob, Ph.D.

Director National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

niaaa: current and future priorities · primary goal of coga: to find and understand genes that...

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