Open Society and Genomics-Enabled Open Society and Genomics-Enabled Personalized MedicinePersonalized Medicine

Tom CurranTom Curran

Deputy Scientific DirectorDeputy Scientific Director

Children’s Hospital of PhiladelphiaChildren’s Hospital of Philadelphia

GENES USGENES USThe Impact of Genomics on Childhood DiseaseThe Impact of Genomics on Childhood Disease

Genes Provide Each Child with Potential that is Shaped by their Environment

The Human GenomeThe Human Genome

• Each person has about 100 trillion cells each containing a complete DNA copy of the genome

• DNA is packed into 46 human chromosomes

• The Human Genome comprises about 25,000 genes

• Genes consist of a specific DNA sequence

• A total of 3 billion base pairs are wrapped up tightly in every cell

“Genomics” is the scientific study of the whole genome

DNADNA

RNARNA

ProteinProtein

genesgenes

makemake

RNARNA

which makewhich make

proteinsproteins

What do Genes do?What do Genes do?

…and proteins make people

DNA: The Double HelixDNA: The Double Helix

AA T T

CC G GWe differ in only 10 million We differ in only 10 million base pairs out of 3 billionbase pairs out of 3 billion

(99.7% identical)(99.7% identical)

Analyzing the Genome: DNA is like a zipperAnalyzing the Genome: DNA is like a zipper

Making a gene chipMaking a gene chip

Glue little pieces of DNA onto glassGlue little pieces of DNA onto glass

Many timesMany times

Link a light bulb to small pieces of DNALink a light bulb to small pieces of DNA

Let them zip upLet them zip up

Let them zip upLet them zip up

Turn out the lightsTurn out the lights

Do it 1 million times and you have a genome chip!

AutismAutism

DiabetesDiabetes

CancerCancer

BlindnessBlindness

Genome ChipsGenome Chips on more than 70,000 children at on more than 70,000 children at CHOP discovered genes contributing to…CHOP discovered genes contributing to…

Dr. Hakon Hakonarson, CHOPDr. Struan Grant, CHOP

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The DNA sequence of the Human Genome: A Rosetta Stone for Medicine

• Predicts risk of disease• Identifies carriers• Matches therapy to patient• Uncovers cause of disease• Offers new treatments

Let me give some examples of the impact of Genomics on children

LancelotLancelot

Leber Congenital AmaurosisLeber Congenital Amaurosis

A rare form of blindness A rare form of blindness caused by a gene mutation. caused by a gene mutation. Gene therapy can restore the Gene therapy can restore the normal gene back into eye normal gene back into eye cells. Affects dogs and cells. Affects dogs and humans. Lancelot was the humans. Lancelot was the first to be treated.first to be treated.

Curing Blindness by Gene TherapyCuring Blindness by Gene Therapy

Light

Retinacells

Inject a corrected version of the mutant gene directly into the retinal cells that don’t work

Dr. Jean Bennet, U PennDr. Jean Bennet, U PennDr. Al Maguire, U Penn Dr. Al Maguire, U Penn Dr. Kathy High, CHOPDr. Kathy High, CHOP

Seeing Lancelot for the first timeSeeing Lancelot for the first time

Preventing Sickle Cell AnemiaPreventing Sickle Cell Anemia

Sickle Cell AnemiaSickle Cell Anemia• One of the most common blood diseasesOne of the most common blood diseases

• Almost exclusively in African-Americans Almost exclusively in African-Americans

• Genetic diseaseGenetic disease

Sickle Cell AnemiaSickle Cell Anemia

Genetic screen then Genetic screen then In Utero In Utero TransplantTransplant fools the fetus to fools the fetus to accept Mom’s bone marrowaccept Mom’s bone marrow

Genetic screen then Genetic screen then In Utero In Utero TransplantTransplant fools the fetus to fools the fetus to accept Mom’s bone marrowaccept Mom’s bone marrow

Ultrasound guided injectionUltrasound guided injectionUltrasound guided injectionUltrasound guided injection

12 to 14 weeks12 to 14 weeksGestation Gestation

12 to 14 weeks12 to 14 weeksGestation Gestation

In Utero Transplantation In Utero Transplantation

Taylor never had to go into a bubble- his blood system came from his Mom

Dr. Alan Flake, CHOP

Taylor never had to go into a bubble- his blood system came from his Mom

Dr. Alan Flake, CHOP

14 yo healthy male14 yo healthy male14 yo healthy male14 yo healthy male

No hospitalizationsNo hospitalizationsNo hospitalizationsNo hospitalizations

No serious infectionsNo serious infectionsNo serious infectionsNo serious infections

Preventing Boy-in-the-Bubble disease: Lethal Genetic Disorder - XSCID

Preventing Boy-in-the-Bubble disease: Lethal Genetic Disorder - XSCID

Cancer is Caused by Gene Mutations

MutationMutation

1 : 3,000,000,000 error1 : 3,000,000,000 error

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Dr. John Maris, CHOPDr. John Maris, CHOPDr. Yael Mosse, CHOPDr. Yael Mosse, CHOP

Drug already Drug already developed for adult developed for adult leukemia now in leukemia now in clinical trial for clinical trial for NeuroblastomaNeuroblastoma

Mutation Mutation discovered discovered in 2008in 2008

Cancers that look the same…

..may have different mutations and they may ..may have different mutations and they may need different treatmentsneed different treatments

11

5050

CancersCancers

GenesGenes 11 25,00025,000

Cancer Targets identified on a Gene CHIPCancer Targets identified on a Gene CHIP

30% of Medulloblastoma patients match the profile

New Brain Tumor New Brain Tumor Drug Based on Drug Based on Plant ToxinPlant Toxin

No treatmentDrug given twice daily by mouth for two weeks

Works 100% of the time in mice Works 100% of the time in mice Works 100% of the time in mice Works 100% of the time in mice

Clinical trial in children starts in 2009 Clinical trial in children starts in 2009 Clinical trial in children starts in 2009 Clinical trial in children starts in 2009 GDC-0449 in Treating Young Patients With Medulloblastoma GDC-0449 in Treating Young Patients With Medulloblastoma That is Recurrent or Did Not Respond to Previous TreatmentThat is Recurrent or Did Not Respond to Previous Treatment

• Gene therapy for genetic disordersGene therapy for genetic disorders

• Early diagnosis and preventionEarly diagnosis and prevention

• Match pediatric disease to existing adult therapiesMatch pediatric disease to existing adult therapies

• Identify new gene targets and develop novel Identify new gene targets and develop novel drugsdrugs

Expensive, takes time, specialized research, collect Expensive, takes time, specialized research, collect lots of information on many children, large number of lots of information on many children, large number of therapies for each disease affecting limited population.therapies for each disease affecting limited population.

GenesRUs:GenesRUs:Personalized Medicine for ChildrenPersonalized Medicine for Children

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