PRECISION MEDICINE –
PHARMACOGENOMICS
Ily”s Kinga
PhD student
Faculty of Pharmacy
Department of Pharmaceutical Technology and
Biopharmacy
University of Medicine and Pharmacy Iuliu Ha”ieganu,
Cluj-Napoca
Introduction
‘ Precision = Personalized = Individualized
‘ Pharmacogenomics ‘ Genetic medicine
‘ Establishing the clinical care based on the individual’s genetic
information and biomarker profile
‘ P5 medicine
‘ Preventive factors measured within a population ” establish
preventive measures for at-risk individuals ” personalized and
participatory healthcare
‘ Survey, monitor and diagnose RISK
‘ Establish SPECIFIC treatment, OPTIMAL drug selection
‘ Treat the patient not the disease
Challenges of the
current healthcare
‘ Genetic polymorphism + biomarkers ” disease
variability
‘ Elevated risk of low therapy effectiveness and
security
‘ Negative financial
implications
‘ Disease costs
‘ Clinical trial failures
(80-90%)
‘ Drug retrievals
Opportunities &
Applications
” the need of therapy individualization
‘ Optimal drug selection based on
‘ Medical and familial history
‘ Genetics/genomics
‘ Exposome
‘ Omics ” gene mapping (HapMap), gene sequencing, identification of
SNPs” disease diagnosis
‘ Preventive approach less financial implications
‘ Shared decision making in the therapy selection ‘ trust and
perception regarding the heathcare system ” indirect + effect on the
therapeutic outcomes
‘ Biobanks if linked to Electronic Medical Records ” translation of
genotype-phenotype data to clinical care (challenges patient
confidentiality)
‘ ‘ knowledge in drug development + better clinical trial design ‘ risk
of failure pre and post marketing of drug
Diagnostic tools (1)
‘ Biomarkers
‘ Biological measures of a biological state
‘ Microarray
‘ Lab-on-a-chip
Diagnostic tools (2)
‘ DNA chips (screenning up to
100000 SNPs in a few hours ”
diagnose phenotypic variations)
‘ Eg. DMET Plus (Affymetrix) ‘ 1936
genetic variants across 231 relevant
genes, including 100% coverage of the
PharmaADME genes (32)
and 95% of
the PharmaADME Core Markers ”
predictory of the pharmacokinetic
variability ” improve drug
development process (effectiveness’,
safety’)
Pharmocogenomics in
drug development (1)
Pharmocogenomics in
drug development (2)
‘ SNPs in the genes of disease, drug transport, drug
metabolism, drug target ” identify genomic
markers ” predict disease response to drug
‘ Pharmacogenetics used for in vitro-in vivo
correlations ” better clinical trial design
‘ Pharmacogenomics ‘ drug labeling
Eg. Genomic data ” expression level of CYP3A gene ” anticipate effect of drugs
like Tacrolimus (immunosuppresiv)
idem CYP2D6 ” Tamoxifen (anticancer agent, selective estrogen modulator)
Idem CYP2C9 ”Warfarin (anticoagulant)
Idem HLA-B*5701 ” Abacvir (antiretroviral) hypersensitivity biomarker
The influence of
pharmacogenetics on plasmatic
concentrations
Old vs new approach in
drug/dose selection
Challenges in the
implementation
Current healthcare regulations
regarding genetic testings (1)
1. Laissez-Faire
‘ Users have full freedom to request new tests and
disclose the results
‘ Heath providers can discriminate their users
according to their genetic risk
‘ Applied in: Australia, Canada, China, Japan, Ireland,
Korea, Russia, Portugal, Spain, South Africa
2. Disclosure Duty
‘ Users cannot be required to take the test
‘ Results can’t be disclosed
‘ Discrimination ‘
‘ Applied in Germany, New Zealand, UK
Current healthcare regulations
regarding genetic testings (2)
3. Consent Law
‘ Users can keep private or disclose the results (for
lower insurance premium)
‘ Discrimination ‘
‘ Applied in Switzerland, Netherland
4. Under strict prohibition
‘ Healthcare providers cannot use the genetic
information for rating
‘ Discrimination ‘
‘ Applied in Austria, Belgium, France, Israel, Italy,
Norway, USA
Conclusion
‘ The right treatment to the right person at a right
dose
‘ Human genome project
”Drug Design ” individualized therapy
”Improved, early diagnosis
”Measurement of disease predisposition
”Disease course monitoring
‘ Under evaluation ‘ challenges regarding
implementation ” lack of a harmonized
healthcare regulation
References
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Thank you!
If it were not for the great variability
among individuals, medicine might as well
be a science and not art. (Frueh, 2005)