niaaa: current priorities and future goals · niaaa extramural grant portfolio, fy 2014 . total...

NIAAA: Current Priorities and Future Goals

George F. Koob, Ph.D.Director

National Institute on Alcohol Abuse and AlcoholismNational Institutes of Health

Friends of NIAAA Annual MeetingMay 12, 2015

2014:• Courtesy visits with members of Congress• Congressional briefing on new horizons in treatment of

alcohol use disorder• Joint Congressional briefing on the impact of substance use

on adolescent brain development

2015:• Congressional briefing on Fetal Alcohol Spectrum Disorders

Thank you for supporting and promoting NIAAA’s mission and work.

Cost and Scope of Addiction

1.1

13

30.5

16.6

0 20 40

HIV/AIDS

Cancer

Drug & Tobacco

Alcohol

Millions in the USPrevalence

36

202

316

223

0 200 400

HIV/AIDS

Cancer

Drug & Tobacco

Alcohol

Billions of dollarsCost to society

Alcohol Effects Across the Lifespan

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

Alcohol

PrenatalAlcohol

Exposure

Underage / BingeDrinking Organ

Damage

MedicationInteractions

Alcohol Use Disorder

AlcoholicFamily

Environment

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

NIAAA Extramural Grant Portfolio, FY 2014 Total Funding $330M, 960 projects

• International Research• Mechanisms of

Behavior Change• Underage Drinking

NIAAA Trans-Divisional Research Emphasis Areas• Biomarkers• Fetal Alcohol Spectrum

Disorders• Genes and Environment

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

Key NIAAA Initiatives and Programs

1. Fetal Alcohol Spectrum Disorders – Prevention & Early Diagnosis

2. Underage and Binge Drinking – N-CANDA, ABCD, CollegeAIM

3. Treatment – Medications Development

4. Co-Morbidities – PTSD

5. Alcoholic Liver Disease

6. Alcohol and HIV/AIDS

7. Alcohol Biosensors

Fetal Alcohol Spectrum Disorders (FASD) Facial Features Correlate with CNS Deficits

Negative correlations between brain volume and lipometer scores after controlling for scan location, age, sex, and ICV in subjects with FASD. (N=52)

Roussotte, F. F., Sulik, K., Mattson, S. N., Riley, E. P., Jones, K. L., Adnams, C.,et al. Human Brain Mapping, 33(2012) 920-37

LipometerScore

With permission Lebel & Sowell

Progress in Fetal Alcohol Spectrum Disorders

• Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)• A multidisciplinary consortium of domestic and international projects focused on

FASD prevention, diagnosis, and intervention.

• CIFASD researchers have developed 3D photography and imaging techniques to enhance the detection of a broad range of facial changes caused by prenatal alcohol exposure in children who have cognitive impairments but lack the hallmark facial features associated with FAS.

• Software is being developed to enable use of hand-held cameras to acquire images.

• Improved identification of prenatal alcohol exposure could lead to earlier intervention and improved treatment outcomes for affected children.

• Collaboration on FASD Prevalence (CoFASP)• A research consortium focused on establishing a more precise and representative

prevalence estimate of FASD among school-aged children in several U.S. communities in California, North Carolina, and the Northern Plains, using active case ascertainment methodology.

• A recent study has estimated the prevalence of FAS in a representative U.S. Midwestern community in the U.S. to be higher than older, previously accepted estimates generated from less representative samples that did not use case ascertainment (6-9 cases/1,000 vs. 2 cases/1,000).

National Consortium on Alcohol and Neurodevelopment in Adolescence

(N-CANDA)

• Multisite longitudinal study of more than 800 youth ages 12-21 using advanced brain images and other tools

• Objectives:– To elucidate the short- and long-tem effects of alcohol exposure

on the developing brain– To identify brain structural and functional anomalies that result

from alcohol exposure as well as predict onset of AUD and otherpsychopathology

• N-CANDA has generated a number of recent research findings including evidence that youth who drink heavily show structural abnormalities in the frontal cortex of the brain

• N-CANDA’s success demonstrates that the much larger Alcohol Brain Cognitive Development (ABCD) Study can be done successfully

NCANDA Data Pipeline and AnalysisClinical, Neuroimaging, and Neuropsychological Assessment

Sex Differences

Tota

l G

ray

Mat

ter

Volu

me

AgeSex Similarities

Tota

l Cor

tical

Th

ickn

ess

Age

Neuropsychological Testing• 8 functional domains

• 25 tests• >1000 measures

AgeAge

Stroop testing "on land" (N=621)

Stroop testing in the scanner (N=268)

e.g., Stroop Match-to-Sample• response inhibition

• bottom-up top-down control

Sample as of September 2014Baseline 7881 year follow-up 303

Age

>1000 clinical and descriptive measures

Harmonize Measurement across Sites

Age

Frac

tiona

l Ani

sotr

opy

(FA

)Fr

actio

nal A

niso

trop

y (F

A)

Correction factor applied to reduce scanner variance

Structural MRI

Diffusion Tensor Imaging (DTI)

Resting-state functional MRI

Adolescent Brain Cognitive Development (ABCD) Study

• Collaborative effort of NIH ICs through the Collaborative Research on Addiction at NIH (CRAN) initiative

• Multisite longitudinal study of 10,000 adolescents who will be recruited prior to the initiation of substance use and followed over 10 years

• Will assess the short- and long-term effects of alcohol and other substance misuse, alone and in combination, on adolescent brain and cognitive development, functional outcomes and individual trajectories

• 3 FOAs issued in February 2015 for an overall coordinating center, research project sites, and a central data analysis center; applications will be reviewed in summer 2015

College Alcohol Interventions Matrix (CollegeAIM)

• Binge drinking and high intensity drinking remain a significant problem among college students.

• 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 “decision support system” to help colleges and universities select appropriate strategies to meet their alcohol intervention goals.

• This decision tool, the College AIM, will allow users to search for strategies according to intervention level (e.g., individual, group, campus-wide, community) and evaluate factors such as effectiveness, cost, and ease of implementation

• CollegeAIM is being finalized and is scheduled for release in September 2015 with participation from the NIAAA College President’s Working Group (current membership – 13 presidents)

NIAAA Medications Development ProgramNIAAA Clinical Investigations Group (NCIG) streamlines the medications development process by bridging the gap betweenpreclinical studies and expensive, time-consuming Phase 3 trials. NCIG:

• facilitates quick turnaround on studies (1½ years)• has access to many CNS compounds through collaborations

with the pharmaceutical industry

• recently completed a trial of a vasopressin antagonist

• in May 2015 will be launching a clinical trial of the widely prescribed anticonvulsant gabapentin

NIAAA’s intramural program also conducts clinical studies on novel compounds with AUD treatment potential.

NIAAA also focuses on disseminating information about treatment options to health professionals and the general public.

Co-morbidities: Alcohol Use Disorder and Post-traumatic Stress Disorder

• The severe adjustment problems often associated with exposure to trauma have drawn attention to the frequent and problematic co-morbidity of alcohol misuse and post-traumatic stress disorder (PTSD).

• This is particularly noted in military personnel associated with the wars in Iraq and Afghanistan. 10-20% of these military personnel meet criteria for PTSD and ~ 30% of this group meet criteria for alcohol misuse.

• NIAAA is seeking to better understand the relationship between AUD and PTSD, and to develop interventions to prevent and treat these disorders.

• For example, NIAAA will be expanding research on the neurobiological mechanisms that underlie co-occurring PTSD and AUD, e.g. the brain’s stress systems, and exploring collaborative opportunities.

• NIAAA sponsored a basic research symposium on the topic at the Society for Neuroscience meeting in 2014 and will be sponsoring a clinically focused session at the 2015 American College on Neuropsychopharmacology.

NIAAA is Addressing Alcoholic Liver Disease

• In 2013, of the 71,713 total liver disease deaths among individuals aged 12 and older, 46.4% involved alcohol.

• Among all cirrhosis deaths in 2011, 48.0% were alcohol related.

• The proportion of alcohol-related cirrhosis was highest (72.7%) among decedents ages 25–34, followed by decedents aged 35–44, at 70.3%.

• In 2009, alcohol-related liver disease (ALD) was the primary cause of almost 1 in 3 liver transplants in the United States.

• NIAAA supports basic and translational research on the pathogenesis of ALD and is exploring novel therapeutic targets for ALD treatment.

• NIAAA supports four alcoholic hepatitis (AH) research consortia that are collaborating to expedite the translation of basic research into improved treatments for AH.

Building a New Research Program for Alcoholic Hepatitis

David W CrabbNaga P Chalasani

Arun J SanyalVijay H Shah

Translational Research and Evolving Alcoholic Hepatitis

Treatment (TREAT)

Ramon BatallerPhilippe Mathurin

Bernd SchnablDavid Brenner

Robert SchwabeWajahat Mehal

InTeam Consortium

Timothy R MorganZhang-Xu Liu

Samuel W FrenchChad P GarnerDavid G Camp

Southern California Alcoholic Hepatitis Consortium

Gyongyi SzaboArthur McCullough

Mack MitchellLaura E Nagy

Craig J McClain

Defeat Alcoholic SteatoHepatitis

(DASH)FY12

FY13

ALCOHOL

systemic metabolic disorders

metabolic liver disorders

Lipopolysaccharides (LPS)[Endotoxemia]

Cytokines: IL8, IL1, IL6TNFα

Gut permeability

Kupffer cell activation

(Modified from Haber et al. 2002)

Malnutrition

Impaired DNA synthesis and

dysregulation ofcell signalling

Dietary Imbalance

STATs

Stellate cell activation

Toxic alcohol metabolites

NADH:NAD

ADHCYP2E1

Acetaldehyde

Adducts

Oxidative Stress

Multi-Factorial Pathogenesis of ALD

NIAAA Research on Alcohol and HIV/AIDS

• Alcohol misuse contributes to the spread of HIV/AIDS world-wide.

• Alcohol misuse also affects HIV/AIDS treatment, e.g. by affecting medication adherence.

• NIAAA supports research in the U.S. and globally to:

– Characterize the role of alcohol misuse in the acquisition, transmission, and progression of HIV

– Translate research findings into effective, culturally appropriate interventions

• NIAAA is working collaboratively with the NIH Office of AIDS Research on these important issues.

NIAAA Alcohol Biosensor Program• Wearable, continuous alcohol monitoring devices are

commonly used in criminal justice and other settings.• Continuous alcohol monitoring is also important for individuals

with ALD or other medical conditions exacerbated by alcohol, e.g. HIV/AIDS and Hepatitis C.

• NIAAA issued a public challenge to stimulate design and production of a non-invasive, wearable device to monitor blood alcohol levels in real time.

• The device should be inconspicuous, low profile, and appealing to the wearer. The design can take the form of jewelry, clothing, or any other format located in contact with the human body.

• The challenge will close in December 2015 and winners will be announced in February 2016.

• Prizes: $200,000 (1st place), $100,000 (2nd place)• NIAAA also supports an alcohol biosensor SBIR/STTR initiative.

NIAAA Alcohol Biosensor Challenge

NIAAA: The Source for Credible Science Information on Alcohol Across the Lifespan

Where We Want to Be1. FDA approval for medications for treatment of alcohol use

disorder (AUD)2. Implementation of effective behavioral treatments for AUD3. Implementation of effective prevention strategies for

adolescent drinking4. Implementation of effective prevention strategies for drinking

during pregnancy5. Elimination of alcohol-related HIV pathology6. Establishment of effective treatments for fetal alcohol

spectrum disorders (FASD)7. Development of effective treatments for alcoholic liver disease8. Appropriate treatment of co-morbidities associated with AUD9. 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

George F. Koob, Ph.D.Director

National Institute on Alcohol Abuse and AlcoholismNational Institutes of Health

Thank You!

niaaa: current priorities and future goals · niaaa extramural grant portfolio, fy 2014 . total...

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