Genomics Changing the Way Care is Delivered

Transcription

1 Genomics Changing the Way Care is Delivered Eric P. Hoffman, PhD Director, Center for Genetic Medicine Research A. James Clark Professor of Molecular Genetics Children s National Medical Center Washington, DC

2 Job Description Provide some in the trenches examples from District of Columbia Children s Hospital showing current and future opportunities in improving health

3 Three Examples The Now #1: Personalized drug development Dr. Guttmacher: Only 2.5% of genes have drugs; what about the others? The Now #2: Nextgen sequencing diagnostics Dr. Guttmacher: The incredible pace of genomics; how can we leverage this to reduced cost of healthcare? The Future: Anticipatory pediatric medicine Dr Guttmacher: The rising incidence of chronic health conditions starting in children; What can we do about them?

4 The Problem Duchenne muscular dystrophy Most common single gene disorder worldwide Focus of Jerry Lewis Telethon MDA Gene: An early deliverable of human genome project

5 The Problem Typical gene: one recipe in a cook book (letter for letter) 30,000 letters (bp) But just 1,000 letters actual ingredients 29,000 letters instructions and advertising Figuring out what is wrong and fixing it is tenable Dystrophin gene 2,300,000 letters (bp) 14,000 letters of ingredients 2,285,000 letters of instructions and advertising

6 The Solution Go in and mess with the cake mix to adjust for missing ingredients

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8 Golden Retriever Muscular Dystrophy (GRMD) NORMAL GRMD Purinacare.com GRMD dogs become progressively weak and develop postural abnormalities Photos courtesy of Joe Korne

9 Recovery of Dystrophin Expression After Systemic Morpholino Treatment in CXMD CXMD Non-treated CXMD Treated: Cocktail morpholinos (5 inj x 120 mg/kg in total) Tibialis Anterior Tibialis Anterior (Right) Tibialis Anterior (Left) Sternocleidomastoid Wild-type beagle Tibialis Anterior Diaphragm Dystrophin (Dys-1) and nuclear staining at 15 days after 5 x injections with 6 g of morpholinos in total targeting exon 6 and 8 (cocktail of Ex6A, Ex6B, Ex8A) into young adult CXMD. Bars; 100 mm

10 Running Test of Littermates Non-treated Littermate 11x Weekly Treated Littermate Non-treated littermate

11 Three Examples The Now #1: Personalized drug development Dr. Guttmacher: Only 2.5% of genes have drugs; what about the others? The Now #2: Nextgen sequencing diagnostics Dr. Guttmacher: The incredible pace of genomics; how can we leverage this to reduced cost of healthcare? The Future: Anticipatory pediatric medicine Dr Guttmacher: The rising incidence of chronic health conditions starting in children; What can we do about them?

12 The Problem DMD is one type of disease causing muscle weakness There are now more than 100 genes known to cause muscle weakness Includes the largest and most complex genes known Duchenne: 2.3 million base pairs (the biggest) Titin (356 different sub-recipes [exons]) A new patient comes to MDA clinic with weakness Molecular diagnostic odyssey Lots of different labs worldwide testing different genes Expensive ($1,000-$3,000 a gene) Can take years and >$20,000 to come up with a genetic diagnosis

13 The Solution Next generation (nextgen) sequencing Currently testing 50 genes in one reaction (1,800 individual pieces) 2 million miniature bubble test tubes per patient in an hour Exomes sequence all recipes in genome at once MDA clinics 200 throughout USA Network established with: MDA National Office MDA clinics (initially 13 major sites) Testing Centers (Emory, Children s National) Do all genes for the cost/time for a single gene

14 Three Examples The Now #1: Personalized drug development Dr. Guttmacher: Only 2.5% of genes have drugs; what about the others? The Now #2: Nextgen sequencing diagnostics Dr. Guttmacher: The incredible pace of genomics; how can we leverage this to reduced cost of healthcare? The Future: Anticipatory pediatric medicine Dr Guttmacher: The rising incidence of chronic health conditions starting in children; What can we do about them?

15 Immune Disorders and Childhood Obesity Getting Much More Common; Leading to Increasing Chronic Disease as Adults District of Columbia has the highest rates of these nationwide Asthma Crohn s Diabetes Obesity Bach JF. N Engl J Med 2002;347:911-20

16 DC Children s - Anticipatory Medicine Anticipating health problems, and providing remedies before the problem arises Identifying the earliest risk factors for disease prior to the disease onset and using these in interventions to prove disease prevention Leveraging emerging technologies from handheld apps, to imaging, to genetics to effect a change from treating symptoms to preventative care

17 DC Children s - Anticipatory Medicine Clark Family Foundation Engineering Healthier Futures for Children: A Systems Biology Approach to Personalized Medicine Asthma - lung disease Inactivity/obesity type 2 diabetes Kidney disease

18 Approach Asthma = AsthMAP Understand the relationship between genes, lung, environment Build engineering systems models attaching math to biology New drugs to synchronize biology Inactivity obesity = CHIP, AIMMY AIMMY Diverse universities in USA and Canada CHIP Schools of 5th graders in Michigan, Maine Determine markers in the blood that predict disease decades later Intervene as children to bring those markers back into line (e.g. preventative maintenance; before it is a major problem)

19 Three Examples The Now #1: Personalized drug development Dr. Guttmacher: Only 2.5% of genes have drugs; what about the others? The Now #2: Nextgen sequencing diagnostics Dr. Guttmacher: The incredible pace of genomics; how can we leverage this to reduced cost of healthcare? The Future: Anticipatory pediatric medicine Dr Guttmacher: The rising incidence of chronic health conditions starting in children; What can we do about them?