Pharmacogenetics in Substance Abuse Clinical Research Gregg Wright

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Pharmacogenetics in Substance Abuse Clinical
ResearchGregg Wright
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Company Profile
IMC Headquarters Reston, VA

• Professional services company
• Life sciences, health research and biomedical
  informatics focus
• Established 1981
• 300 US based employees
• Offshore development subsidiary in Pune, India

Offices and Project Team Locations
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Health Research Clients
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Solution Areas

• Biospecimen inventory management
• Clinical research systems and operations support
• Document and digital content management
• Electronic medical record capture and
  standardization
• Microarray data analysis and management
• Patient safety reporting and analysis
• Pharmacogenetics clinical research support
• Science administration
• Scientific systems integration and custom
  solutions
• Semantic applications biomedical ontologies,
  speech recognition, and natural language
  processing

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NIDA Intramural Clinical Research

• Hundreds of community treatment sites
• Thousands of addiction patients
• Hundreds of researchers
• Tens of millions of clinical transactions
• Alternative use studies of approved drugs
• Traditional efficacy, safety focus
• Centralized clinical data warehouse for
  cross-trial analysis
• Incorporating pharmacogenetics

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Long Term Objective

• Pharmacogenetics Understanding how genetic
  variation affects response to therapeutics

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Phase 2 Clinical Trial for Methamphetamine
Dependence

• Trial Summary
• Double-blind
• Placebo-controlled
• 140 subjects (70/70)
• Topiramate treatment
• Daily dosage for 91-days
• Outcome metric meth use
• Pharmacogenetics Component
• Genotype analysis
• Gene expression analysis (three time points)

• Topiramate
• Anti-convulsant approved for epilepsy and
  migraines
• Raises cerebral GABA levels
• Inhibits glutamatergic activity
• Attenuates addiction reward system in rats

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Hypothesis Generating Research

• Gene expression patterns
• SNP patterns
• For Topiramate recipients with positive clinical
  outcome, how do they differ from Topiramate
  recipients with no or negative outcome, in terms
  of
• Gene expression
• SNPs
• Clinical/phenotype characteristics

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Genetics Sample and Data Flows
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Gene Expression Analysis

• Biologys Central Dogma

• Microarray Analysis

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Genotype Analysis

• DNA Normal and with SNP
• (Single Nucleotide Polymorphism)

• SNP Identification

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PAXgene Blood System

• From PreAnalytiX Corp.
• Stabilizes blood at room temperature up to 72
  hours
• Standard Vacutainer collection
• Allows shipping to central lab without freezing
• Globin reduction protocol
• Affymetrix collaboration

Paxgene Blood DNA System
Paxgene Blood RNA System
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Microarrays

• GeneChips
• Expression
• HG U-133 Plus 2.0 array
• Whole genome coverage
• 47,000 transcripts and ESTs
• Used in over 3,000 peer reviewed papers
• Genotype
• Mapping 500K array set
• 500,000 SNP coverage
• Used in over 50 peer-reviewed papers

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Pharmacogenetics Analysis