PHARMACOGENOMICS:

THE PROMISE OF PERSONALIZED MEDICINE

MBB 1 Lecture
April 25, 2013
EMPIRICAL APPROACH ON DRUG THERAPY
EMPIRICAL APPROACH ON DRUG THERAPY
ONE SIZE DOES NOT FIT ALL!
WHAT IS PHARMACOGENOMICS?
• A science that examines the inherited variations in genes that
dictate drug response, and

• Explores the ways these variations can be used to predict

whether a patient will have a good response to a drug, a bad
response to a drug, or no response at all.

• Study of how an individual's genetic makeup affects the body's

response to drugs
OUR GENES DICTATE HOW
DRUGS AFFECT OUR BODY
• Genetic variation influences drug
• Adsorption
• Distribution
• Metabolism
• Elimination
• Interaction with receptor
• Efficacy

• Genetic variation among individuals  different overall

responses towards different drugs and doses
GENOME-TAILORED DRUG
SELECTION AND DOSAGE
Selection of appropriate drug and dose for the individual
patient in order to

• achieve optimal therapeutic response

• avoid therapeutic failure
• minimize side effects and toxicity

 PERSONALIZED MEDICINE
HOW CAN GENETIC VARIATION BE
USED TO PREDUCT DRUG RESPONSE?

Single nucleotide
polymorphisms (SNPs)
 Most common type of DNA
variation
 Occurs in the genome in about 1
in every 300 bases
 Present in at least 1% of the
general population
 Can be used as a diagnostic
tool to predict a person's drug
response
EFFECT OF SNPS
SNPs can result in
subtle differences in
proteins that translate to
major differences in how
the protein functions
CYTOCHROME P450 ENZYME
FAMILY
Enzymes responsible for a major portion of
drug metabolism in humans
WHY SOME DRUGS DON’T WORK IN
SOME PATIENTS

Less active or inactive

forms of CYP enzymes
that are unable to break
down and efficiently
eliminate drugs from the
body can cause drug
overdose in patients

Other variants (non-wild type)

of CYP2C19 gene results in
protein that is unable to convert
clopidogrel to its active form
AMPLICHIP CYP450
ARRAY
DNA microarray / DNA chip

Technology used to examine the

presence of specific SNPs
quickly

The AmpliChip CYP450 will test

for variations in 2 genes:
CYP2D6 and CYP2C19 (which
affect how people process about
25% of drugs in the market)
GENERAL SCHEME FOR THE
AMPLICHIP ARRAY
EXAMPLES OF INHERITED OR ACQUIRED
VARIATIONS IN ENZYMES AND RECEPTORS
THAT AFFECT DRUG RESPONSE
EXAMPLES OF INHERITED OR ACQUIRED
VARIATIONS IN ENZYMES AND RECEPTORS
THAT AFFECT DRUG RESPONSE
PHARMACOGENOMICS OF
WARFARIN
BENEFITS OF
PHARMACOGENOMICS
• Improve drug choices

• Safer dosing

• Decrease in healthcare costs

• Improvement in drug development

BARRIERS TO
PHARMACOGENOMICS
• Complexity of finding gene variations that affect drug response

• Limited drug alternative

• Unwillingness of drug companies to develop alternative drugs

for only a small population