NIAAA Extramural Advisory Board Report

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NIAAA Extramural Advisory Board
Report Medications Development Feb. 8-9, 2005
Fulton T. Crews UNC Chapel Hill
NIAAA Council Meeting May
26, 2005
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PARTICIPANT LIST
Medications Development Team Co Leaders
Mark
Egli Raye Litten
Medications Development Team Members Ann Bradley
Lisa NeuholdKendall
Bryant Antonio
NoronhaPage Chiapella
Harold PerlJoanne Fertig
Vishnu Purohit Laurie Foudin
Deidra Roach Tom Gentry
Denise Russo Ted George
Peter SilvermanQ. Max Guo
Roger
SorensenMarcus Heilig
Robert Taylor David Herion
Dennis TwomblyMike Hilton
John UmhauRobert Huebner
Mark Willenbring George Kunos
Sam Zakhari Patricia Lake
David Lovinger
ConsultantsCherry Lowman
Charlie GrudzinskasMargaret
Mattson Bill
Corrigall Howard Moss
Research Strategies Committee (RSC) Ting-Kai
Li Stephen Long Faye Calhoun Mark
Goldman Kenneth Warren Howard Moss
Extramural Advisory Board (EAB) John Crabbe
Bankole Johnson Fulton Crews (Chair) Peter
Monti Cindy Ehlers Kenneth Sher (rep.
NIAAA Adv. Council) Tom Greenfield Linda
Spear Andrew Heath
Invited Experts Linda Brady Craig
McClain Walter A. Brown Stephanie
OMalley Ivan Diamond Bruce G.
Pollock Howard J. Edenberg James P. Stables
George F. Koob Alan C. Swqnn John
Littleton Boris T. Tabakoff Barbara
J. Mason Stanley S. Wallack David J.
McCann David T. Wong
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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 1 Establish a coordinated infrastructure and
  network of animal model laboratory testing and
  provide for the development of human laboratory
  model development.
• 2 Establish a flexible and open clinical
  infrastructure that includes testing medications
  in various stages of alcohol use disorders and
  comorbidity using standardized core instruments.
• 3 Create ascientific advisory board that
  provides guidance and coordination of medications
  development as well as promoting translational
  research.
• 4 Indentify predictive biological and
  developmental markers (including DNA) for
  identifying patients and characterizing disease
  progression and treatment response to candidate
  medications.
• 5 Identify and validate molecular targets for
  medications development at various stages of the
  disease.

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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 1 Establish a coordinated infrastructure and
  network of animal model laboratory testing and
  provide for the development of human laboratory
  model development. Several paradigms of animal
  and human laboratory models are needed for
  screening of lead compounds as no one model is
  likely to be predictive for all facets of alcohol
  use disorders. Medications with known clinical
  efficacy should be tested in all models. A mix
  of established models and new models (e.g. higher
  throughput, primates, early stages of drinking)
  is needed. Human laboratory models can be a
  valuable bridge between animal and human studies
  and should be further developed. Commonality of
  methods and replication across sites is
  essential.

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Preclinical Animals Modelsfor Medication
Development
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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 1 Establish a coordinated infrastructure and
  network of animal model laboratory testing and
  provide for the development of human laboratory
  model development.
• 2 Establish a flexible and open clinical
  infrastructure that includes testing medications
  in various stages of alcohol use disorders and
  comorbidity using standardized core instruments.
• 3 Create a scientific advisory board that
  provides guidance and coordination of medications
  development as well as promoting translational
  research.
• 4 Identify predictive biological and
  developmental markers (including DNA) for
  identifying patients and characterizing disease
  progression and treatment response to candidate
  medications.
• 5 Identify and validate molecular targets for
  medications development at various stages of the
  disease.

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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 2 Establish a flexible and open clinical
  infrastructure that includes testing medications
  in various stages of alcohol use disorders and
  comorbidity using standardized core instruments.
  Since many compounds are promising for multiple
  disorders, investigate possible collaborations
  with other NIH institutes in conducting clinical
  trials. Since most of the diagnosis of alcohol
  dependence occurs before the age of 26, include
  testing with young adults and where possible with
  adolescents. Establish core effectiveness
  assessment and standardized endpoint measurements
  before implementing the clinical trials network.
  Employ a network infrastructure for efficient use
  of resources and time.

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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 3 Create a scientific advisory board that
  provides guidance and coordination of medications
  development as well as promoting translational
  research. Include basic and clinical researchers
  on advisory board and representatives from
  industry.

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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 4 Identify predictive biological and
  developmental markers (including DNA) for
  identifying patients and characterizing disease
  progression and treatment response to candidate
  medications. Partner with high-tech companies.
  Use biomarkers for screening lead compounds.
  Explore patterns of new biomarkers using
  high-throughput technologies in genomics,
  proteomics, and metabolomics

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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 5 Identify and validate molecular targets for
  medications development at various stages of the
  disease. Determine molecular targets that
  overlap with various psychiatric and substance
  abuse co-morbidities. Continue to support
  research in identifying neurocircuits and
  molecular and cellular mechanisms underlying
  alcohol-seeking behavior and drinking that may
  lead to new molecular targets of drug discovery

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NIAAA EAB RECOMMENDATIONS FOR MEDICATIONS
DEVELOPMENT

• 1 Establish a coordinated infrastructure and
  network of animal model laboratory testing and
  provide for the development of human laboratory
  model development.
• 2 Establish a flexible and open clinical
  infrastructure that includes testing medications
  in various stages of alcohol use disorders and
  comorbidity using standardized core instruments.
• 3 Create ascientific advisory board that
  provides guidance and coordination of medications
  development as well as promoting translational
  research.
• 4 Indentify predictive biological and
  developmental markers (including DNA) for
  identifying patients and characterizing disease
  progression and treatment response to candidate
  medications.
• 5 Identify and validate molecular targets for
  medications development at various stages of the
  disease.