Governor’s Vision Conference on Personalized Medicine

Governor’s Vision Conference on Personalized Medicine December 6, 2006 Stephen M. Prescott M.D. What is “Personalized Medicine”? Multiple names for similar concepts: •Predictive Medicine •Individualized Medicine •Information-based Medicine Common Goals: •Increase the efficacy of treatment •Minimize side effects •Improve cost-efficiency The Need for Improved Therapeutics • Estimated that in the United States alone each year adverse events account for – Over 100,000 deaths – More than 2 million hospitalizations • The effectiveness of prescribed medications ranges from 20-60% Better diagnosis (e.g. with biomarkers) makes existing therapies safer Everyone who receives a therapy is subject to an adverse event, but only a minority benefit If you can predict the responders, you achieve all of the benefit with fewer adverse events Predicting Responsiveness Improves the Overall Outcome of Treatment Responder Nonresponder Patients with same Diagnosis Predicting Adverse Events Improves the Outcome Even More No Toxicity Toxic effect Responder Components of Personalized Medicine Host (patient) Favorable Response or Side Effect Treatment Disease Tissue (target) Is it Real or “Academic” March 2005 – FDA Issues final Pharmacogenomics Guidelines “Pharmacogenomics is a new field, but we intend to do all we can to use it to promote the development of medicines.” - Former FDA Commissioner Mark B. McClellan, M.D., Ph.D. Business Week Magazine “If Amgen could figure out which genes trigger the positive response [to a drug] it might be able to identify a test to identify those patients… and market more precisely, thus lowering costs and boosting sales and profits” - Roger Perlmutter, M.D., V.P., Research and Development, Amgen They’re Already on the Internet! Why a Genetic Approach is Warranted Disease Heart Disease Cancer Stroke Lower Respiratory Disease Adverse Drug Reactions (est) Diabetes # of Deaths* 696,947 557,271 162,672 124,816 106,000 73,249 Genetic Susceptibility? Yes Yes Yes Yes Yes Yes *National Vital Statistics Reports, Vol. 53, No. 17, March 7, 2005 Why Utah? Demographic/epidemiological record already exists (“GeNetwork”) No other population will have a genetic structure Powerful for discovery of mechanism Gene-environment interactions Unparalleled Discovery Assets Quebec (Galileo) Iceland (deCODE) Utah (LineaGen) Wisconsin (Marshfield) Estonia (EGeen) UK (UK BioBank) Key advantages of Utah’s Assets  Most extensive genetic records  Extensively integrated medical records  Largest research institution Inherited Disorder Colon Cancer (Familial Adenomatous Polyposis Coli) Neurofibromatosis Breast Cancer Melanoma Cardiac arrhythmias (Long QT Syndrome) Gene APC NF-1 BRCA-1 BRCA-2 p16 KVLQT1 minK HERG MiRP1 Supravalvular Aortic Stenosis Alport Syndrome Hypertension Macular degeneration (Stargardt’s Disease) Ulnar-Mammary Syndrome ELN COL45A5 XIB AGT ABCR TBX3 Williams Syndrome Porphyria Cutanea Tarda Inflammatory Syndromes Chediak-Higashi Syndrome Neonatal Epilepsy Hyperkalemic Periodic Paralysis Paramyotonia Congenita Potassium Aggravated Myotonia Hypokalemic Periodic Paralysis Periodic Paralysis 3 Andersen’s Syndrome Frings Audiogenic Epilepsy Spinocerebellar Ataxia Type 7 Familial Advanced Sleep Phase Syndrome LIMK1 URO-D PAF-AH CHS-1 KCNQ2 KCNQ3 SCN4A SCN4A SCN4A CACNA1S KCNE3 KCNJ2 Mass1 SCA7 hPer2 Genetic Disorders in Which Molecular Basis Was Discovered at the University of Utah GeNetwork A dynamic linkage of genealogic, demographic, genetic, and clinical information to support medical research at the University of Utah Utah Population Database 6.5 MM Persons (UPDB) The Utah Population Database • • • Over 16 million records Utah and surrounding states Allows either a population or genetic approach simultaneously The Utah Population Database • • • • • • Over 16 million records Utah and surrounding states Allows either a population or genetic approach simultaneously Large pedigrees enable genetics Relational databases with powerful bioinformatics analytical tools 25 year record of ethical management The Integration of Data is Dynamic and Continuous Genealogy Records (1.6 million) Birth Records (2.1 million) Cancer Records (340,000) Death Records (707,000) Drivers Licenses (2.77 million) Marriage & Divorce (784,000) Hospital Clinical Records (>12 million) Comprehensive Medical Records Utah Population Database 6.5 MM Persons (UPDB) Millions of Medical Records (HSC) Comprehensive Medical Records Outpatient Information • ICD9 Diagnoses • Medical History Laboratory Results • Radiology • Pathology Pharmacy Data >1 million person medical records have been linked into GeNetwork Deep Phenotypic and Genotypic Data Phenotype & Genotype Data on Utah Families (UGRP) Utah Population Database 6.5 MM Persons (UPDB) Millions of Medical Records (HSC) Utah Genetic Reference Project • Uses original reference families for the Genome Project – 47 families, 3 generations from Utah so-called “CEPH” set of DNA • Study of the genetic basis of quantitative traits • Emphasis on medically relevant traits 4 Grandparents 2 Parents 8 or More Children Detailed Exams (“Poke and Probe”) • Blood pressure, body temperature, resting pulse • Height and weight measurement • Handedness • BMI, height, weight, body fat measurement • EKG • Assay of skin melatonin • Attention test: T.O.V.A • Anthropometric measurements • Voice pitch • Eye exam • Audiometry • Dental exam • Review of medical records, supine blood pressure, resting pulse • Bone density and mineral content, indirect muscle mass measurements • Taste • Smell • Pitch • Pulmonary Function • Echocardiogram • Serum/plasma reference set for biochemical measurements Extensive Examinations 16 samples donated by each family member are shared among many researchers Patient –Oriented Research Clinics Autoimmune Disorders • Psoriasis • Rheumatoid Arthritis • Multiple Sclerosis Respiratory Disorders • COPD • Asthma Neurological Disorders • Epilepsy • Autism Metabolic Disorders • Osteoporosis • Type II Diabetes • Thought Leaders • Detailed longitudinal records • Biosamples Many others… Research Programs: Data & Biosamples Phenotype & Genotype Data on Utah Families (UGRP) Utah Population Database 6.5 MM Persons (UPDB) Clinical Trials Infrastructure Millions of Medical Records (HSC) Identified Novel Genetic Locus W/O a Single Experiment Mine UGRP Pedigrees for Psoriasis (3) Link to central database Families Enlarged 14-fold How GeNetwork Enables Discovery Utah Psoriasis Initiative Lung Disease Research Clinics Hospital & Clinic records Utah Cancer Registry (SEER) Melanoma Research Clinic Population database Microarray Facility Adverse Events Registry Genetics Reference Project Broad Partnerships Research Repositories: Data & Biosamples Phenotype & Genotype Data on Utah Families (UGRP) Utah Population Database 6.5 MM Persons (UPDB) Clinical Trials Infrastructure Non-Profit Millions of Medical Records (HSC) Corporate Partners Integrated Clinical Network Autoimmune Dx Discovery Therapeutic Target Discovery COPD Biomarker Discovery Governor’s Vision Conference on Personalized Medicine December 6, 2006 Stephen M. Prescott M.D.