Personalized Medicine: What does it mean and why do we want to get there?

Transcription

1 Personalized Medicine: What does it mean and why do we want to get there? Dan M. Roden MD Assistant Vice Chancellor for Personalized Medicine Principal Investigator, BioVU Vanderbilt University Medical Center

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3 AGACTCGCT AGACTAGCT A Single Nucleotide Polymorphism (SNP, or snip )

4 0.5% of all nucleotides: 15,000,000/3 billion A variant can Make us look different Cause a disease (sickle trait, long QT, ) Predispose to a disease if other triggers are present Predispose to an unusual drug reaction Be irrelevant AGACTCGCT AGACTAGCT

5 Hype

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7 Finding common genetic variants that make me susceptible to disease atrial fibrillation heart attack Knowing this might eventually make me smarter about preventive therapy, but not yet (probably) drug metabolism

8 2000: one draft human genome sequence, 10+ years, $2.7 billion 2010: A full human genome in 30 minutes, $1000

9 Hopes: Personalized Medicine 1. How do we choose treatments for our patients? 2. Why an average response might not apply to you: some examples. 3. The vision of Personalized Medicine, and why Vanderbilt is the place to move this concept forward. 4. What are we doing now, and where do we want to go?

10 55 year old Caucasian woman Multiple surgery for lung cancer; recurrent pulmonary nodules What can be done at this point? Best therapy based on experience with current drugs Best therapy based on published clinical trials using current drugs Selecting therapy based on her tumor biology

11 55 year old Caucasian woman Multiple surgery for lung cancer; recurrent pulmonary nodules

12 Medicine 2009

13 Drug metabolism Medicine 2009

14 Medicine 2009 What we tolerate: Premature, predictable, and preventable disease One size fits all medicine Ignoring what we know about inter-individual variability in people, their environments, and their responses to drugs

15 Variable Responses to Drug Therapy

16 How do we go about using genetic variant information in prescribing? "Here's my sequence... New Yorker, 2000

17 Francis Collins, 9/16/2009 "Here's my sequence... New Yorker, 2000

18 What will it take to put in place a comprehensive program in Personalized Medicine? A Personal View Great science Information technology Engaging patients

19 Genotypes: CYP2D6: *4/*4 CYP2C9: wt/*2 NAT: slow TPMT: wt/wt UDPG: 6/6 ACE: ID CETP: BB BRCA1: negative β1 AR: S49/G389 β2 AR: R16/G27 KCNQ1: R583C HERG: wt/wt SLOC1B1 TC B* Apoε: 2/3 VKORC1 A/B

20 Genotypes: CYP2D6: *4/*4 CYP2C9: wt/*2 NAT: slow TPMT: wt/wt UDPG: 6/6 ACE: ID CETP: BB BRCA1: negative β1 AR: S49/G389 β2 AR: R16/G27 KCNQ1: R583C HERG: wt/wt SLOC1B1 TC B* Apoε: 2/3 VKORC1 A/B

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22 Errors per 100 orders Potential ADE Prescribing error Rule violation 0 Pre-computer entry Post-computer entry

23 3,000 2,000 20,000 10,000 60,000 BioVU: a clinical laboratory for Personalized Medicine 120, ,000 80,000 60,000 40,000 20,000 0 Mar-07 Jun-07 Sep-07 Dec-07 Mar-08 Jun-08 Sep-08 Feb-09 Apr-09 Jun-09 Sep-09 Dec-09 Mar-10 Jun-10 Sep-10 Dec-10 Mar-11 Vanderbilt Electronic Systems for Pharmacogenomic Assessment

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25 PGPop: PharmacoGenomic discovery and replication in very large patient POPulations

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27 Vanderbilt Personalized Medicine: Vision Not only The right dose of the right medicine for the right patient at the right time but also: A plan for health that is Personalized Predictive Preemptive Participatory

28 Drug Response The Vanderbilt Patient Encounter: 2019 Heart Attack

29 Implementing this expansive view of Personalized Medicine will require expertise across multiple disciplines Individual content areas Cancer Heart Kids Psych Obesity Alzheimer ICU Diabetes Basic science Information technology and support Interdisciplinary Translation: economics, ethics, Training and outreach