PGFI 2009 Franklin Curran

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  • 1. Open Society and Genomics-Enabled Personalized Medicine Tom Curran Deputy Scientific Director Childrens Hospital of Philadelphia GENESUS The Impact of Genomics on Childhood Disease

2. 3. Genes Provide Each Child with Potential that is Shaped by their Environment 4. 5. The 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

6. DNA RNA Protein genes make RNA which make proteins What do Genes do? 7. and proteins make people 8. 9. 10. 11. 12. DNA: The Double Helix AT CG We differ in only 10 million base pairs out of 3 billion (99.7% identical) 13. Analyzing the Genome: DNA is like a zipper 14. Making a gene chip 15. Glue little pieces of DNA onto glass 16. Many times 17. Link a light bulb to small pieces of DNA 18. Let them zip up 19. Let them zip up 20. Turn out the lights 21. Do it 1 million times and you have a genome chip! 22. 23. Autism Diabetes Cancer Blindness Genome Chipson more than 70,000 children at CHOP discovered genes contributing to Dr. Hakon Hakonarson, CHOP Dr. Struan Grant, CHOP 24. 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 25. Lancelot Leber Congenital Amaurosis A rare form of blindness caused by a gene mutation. Gene therapy can restore the normal gene back into eye cells. Affects dogs and humans. Lancelot was the first to be treated. Curing Blindness by Gene Therapy 26. Light Retina cells Inject a corrected version of the mutant gene directly into the retinal cells that dont work 27. Dr. Jean Bennet, U Penn Dr. Al Maguire, U PennDr. Kathy High, CHOP Seeing Lancelot for the first time 28. Preventing Sickle Cell Anemia 29. Sickle Cell Anemia

  • One of the most common blood diseases
  • Almost exclusively in African-Americans
  • Genetic disease

30. Sickle Cell Anemia 31. Genetic screen thenIn Utero Transplantfools the fetus to accept Moms bone marrow Ultrasound guidedinjection 12 to 14 weeks Gestation 32. In Utero Transplantation 33. Taylor never had to go into a bubble- his blood system came from his Mom Dr. Alan Flake, CHOP Preventing Boy-in-the-Bubble disease:Lethal Genetic Disorder - XSCID 14 yo healthy male No hospitalizations No serious infections 34.

  • Cancer is Caused by Gene Mutations

35. Mutation 1 : 3,000,000,000 error Dr. John Maris, CHOP Dr. Yael Mosse, CHOP Drug already developed for adult leukemia now in clinical trial for Neuroblastoma Mutation discovered in 2008 36. Cancers that look the same ..may have different mutations and they may need different treatments 37. Cancer Targets identified on a Gene CHIP 1 50 Cancers Genes 1 25,000 30% of Medulloblastoma patients match the profile 38. New Brain Tumor Drug Based on Plant Toxin 39. No treatment Drug given twice daily by mouth for two weeks 40. Works 100% of the time in miceClinical trial in children starts in 2009GDC-0449 in Treating Young Patients With Medulloblastoma That is Recurrent or Did Not Respond to Previous Treatment 41.

  • Gene therapy for genetic disorders
  • Early diagnosis and prevention
  • Match pediatric disease to existing adult therapies
  • Identify new gene targets and develop novel drugs

Expensive, takes time, specialized research, collect lots of information on many children, large number of therapies for each disease affecting limited population. GenesRUs: Personalized Medicine for Children R