Personalized Medicine

an oral Seminar, Alexandria University-Egypt

1. Personalized Medicine Dalia A. Hamdy BPSc , MSc, PhD, RP (ACP), MRSC 14 May 2015 d [email protected]

2. Outline Personalized Patient Care Pharmaceutical disciplines involved What is a gene? SNV and SNP P4 Medicine Genetic screening Examples of personalized medication How can we get ready? Personalized Medicine- DH- May 2015 2

3. Personalized Medicine “is the tailoring of medical treatment to the individual characteristics of each patient” The Age of Personalized Medicine “The science of individualized prevention and therapy” National Institute of Health Personalized Medicine- DH- May 2015 3

4. Pharmacokinetics & Pharmacodynamics Personalized Medicine- DH- May 2015 4

5. Metabolic Enzymes and Transporters families Personalized Medicine- DH- May 2015 5

6. Pharmacogenetics T he study of how genes affect a person’s response to drugs Personalized Medicine- DH- May 2015 6 Pharmacology (Science of Drugs) G enomics (Study of genes and their functions) Pharmacogenomics

7. What is a Gene? DNA (deoxyribonucleic acid), the cell’s hereditary material. DNA is a polymer of nucleotides (sugar, phosphate and one of four nitrogenous bases (A,T,G,C ) Personalized Medicine- DH- May 2015 7 DNA Sequence

8. What is a Gene? Human genome consists of about 3.2 billion base pair ( bp ) Every person has two copies of each gene, one inherited from each parent (6.4 billion bp ) DNA molecule is packaged into thread-like structures called chromosomes . 23 pairs of Chromosomes Sex chromosome XX or XY 22 pairs autosomes Personalized Medicine- DH- May 2015 8

9. What is a Gene? The exact function of most of the DNA in the human genome is unknown Protein-coding genes ≈ 2 % Blueprint for the production of proteins (enzymes, structural elements, signaling molecules) Personalized Medicine- DH- May 2015 9

10. What is a Gene? The exact function of most of the DNA in the human genome is unknown Protein-coding genes ≈ 2% Personalized Medicine- DH- May 2015 10

11. SNV and SNP Gene mutations Inherited from a parent A cquired during a person’s lifetime Mutations range in size from single base-pair mutation that occurs at a specific site in the DNA sequence (SNV) to a large segment of a chromosome (CNV) Personalized Medicine- DH- May 2015 11 SNP = SNV which occur in at least 1-2% of the population

12. The Human Genome Project I nternational research effort to determine the sequence of the human genome and identify the genes that it contains F ormally began in 1990 and was completed in 2003 Personalized Medicine- DH- May 2015 12

13. Personalized Medicine- DH- May 2015 13 . Why is Pharmacogenomics and SNP Knowledge important?

14. 1. optimize drug therapy, with respect to the patients' genotype, to ensure maximum efficacy with minimal adverse effects One Size fits all medicine Vs. Personalized medicine Personalized Medicine- DH- May 2015 14

15. 2. E mployment of Gene Therapy an experimental technique that uses genes to treat or prevent disease. Replacing a mutated gene that causes disease with a healthy copy of the gene. Inactivating, or “ knocking out ,” a mutated gene that is functioning improperly. Introducing a new gene into the body to help fight a disease. Promising But still u nder investigation! Personalized Medicine- DH- May 2015 15

16. P4 Medicine “prospective genotyping will lead to patients being prescribed drugs which are both safer and more effective .” AstraZeneca (2000) Personalized Medicine- DH- May 2015 16

17. P4 Medicine “personalized medicine does not literally mean the creation of drugs or medical devices that are unique to a patient but rather the ability to classify individuals into sub-populations that differ in their susceptibility to a particular disease or their response to a specific treatment” The President’s Council of Advisors on Science and Technology (PCAST), 2008. Personalized Medicine- DH- May 2015 17

18. P4 Medicine “Medicine is undergoing a revolution that will transform the practice of health care in virtually every way. This revolution is often termed “personalized medicine”– but this label does not do justice to the multiple dimensions of the coming changes” Dr. Lee Hood, MD, PhD P4Mi Chairman and ISB president Personalized Medicine- DH- May 2015 18

19. P4 Medicine 4P?! Personalized Preventive Predictive Participatory Personalized Medicine- DH- May 2015 19

20. Genetic Screening/Testing Personalized Medicine- DH- May 2015 20 phenylketonuria congenital hypothyroidism Down Syndrome Ethical Concerns! Safety Concerns!

21. NOW the available diagnostic technologies detect a single biomarker or variant in a single gene, advances in analytical techniques whole genome sequencing technologies Personalized Medicine- DH- May 2015 21 Genetic Screening/Testing

22. Alleles and Egyptian Population Warfarin a good candidate for personalized medicine? -Anticoagulant with narrow therapeutic window. - Widely prescribed -High inter patient variability individual in the required dose due to different alleles of the following genes or enzymes CYP2C9 VKORC1 CYP4F2 APOE CALU Personalized Medicine- DH- May 2015 22

23. Alleles and Egyptian Population Warfarin Dosing Personalized Medicine- DH- May 2015 23

24. VKORC1 (1173C>T) contributes to the 20.5% of warfarin dose variability. the warfarin algorithm developed by E gyptian researchers were comparable with those of the IWPC and Gage algorithms with the advantage of using one SNP (VKORC1 1173C>T) only. (for doses>35 mg/week) Personalized Medicine- DH- May 2015 24 Alleles and Egyptian Population

25. FDA 120 FDA approved drugs with Pharmacogenomic Biomarkers in Drug Labeling includes specific actions to be taken based on the biomarker information http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm Personalized Medicine- DH- May 2015 25

26. Drug Therapeutic Area HUGO Symbol Referenced Subgroup Labeling Sections Warfarin Cardiology or Hematology VKORC1 VKORC1 rs9923231 A allele carriers Dosage and Administration, Clinical Pharmacology Warfarin Cardiology or Hematology CYP2C9 CYP2C9 intermediate or poor metabolizers Dosage and Administration, Drug Interactions, Clinical Pharmacology 26 Personalized Medicine- DH- May 2015

27. How can we get ready? Royal Pharmaceutical Society : emphasized the role that pharmacists may play in performing genetic tests (perhaps in collaboration with local physician practitioners) and in counseling patients about the results of tests that are either ordered by their physician or purchased from other sources Academic Affairs Committee of the American Association of Colleges of Pharmacy: drafted recommendations for pharmacy education To include goals for knowledge, skills, and attitudes that pharmacists and student pharmacists should aim to achieve in preparation for potential pharmacist roles in pharmacogenetics Personalized Medicine- DH- May 2015 27

28. How can we get ready? “The new curriculum will prepare students more intensively for the new biology (including cell biology and genetics) and personalized medicine , nanomedicine , pharmacogenomics, and cellular, gene and protein therapies. Other additions include new material on public health, interprofessional education, and leadership education for all students” College of Pharmacy University of Minnesota March 2014 http:// www.pharmacy.umn.edu/news/publications/record_summer13/newcurriculum/index.htm Personalized Medicine- DH- May 2015 28

29. How can we get ready? Run continuing educational sessions to cover the following points Personalized Medicine- DH- May 2015 29 Pharmacy Today. 2008(Feb);14(2):55–66.

30. References Mccarthy , J and Nussbaum, RL. Genomic and Precision Medicine online course. University of California San Fransisco . Through Coursera online courses . Shahin , MHA et al. Pharmacogenet Genomics. 2011 March ; 21(3): 130–135. Ekladious , SM et al. Mol Diagn Ther . 2013 Dec;17(6):381-90. Personalized Medicine- DH- May 2015 30

31. Personalized Medicine- DH- May 2015 31