personalized medicine

PERSONALIZED MEDICINE

Dalia A. HamdyBPSc, MSc, PhD, RP (ACP), MRSC

14 May [email protected]

Personalized Medicine- DH- May 2015 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 “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


Pharmacokinetics & Pharmacodynamics


Metabolic Enzymes and Transporters families


PharmacogeneticsThe study of how genes affect a person’s response to

drugs

Pharmacology(Science of Drugs)

Genomics(Study of genes and

their functions)

Pharmacogenomics


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)

DNA Sequence


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


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)


What is a Gene?•The exact function of most of the DNA in the human genome is unknown

•Protein-coding genes ≈ 2%


SNV and SNP• Gene mutations

• Inherited from a parent• Acquired 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)

SNP = SNV which occur in at least 1-2% of the population


The Human Genome Project • International research effort to determine the sequence of the human genome and identify the genes that it contains

• Formally began in 1990 and was completed in 2003


.

Why is Pharmacogenomics and SNP Knowledge important?


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

http://www.google.com.eg/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=vJT-7FOY4rHyUM&tbnid=fFwL8szl7QBXSM:&ved=0CAUQjRw&url=http://www.tedxvienna.at/blog/personalize-this/&ei=uclcU566Hsi70QWfv4HADA&bvm=bv.65397613,d.ZWU&psig=AFQjCNE3wGYjXASaLuiEJP5YBN5eVujTQQ&ust=1398676249499503


2. Employment 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 under investigation!


P4 Medicine

“prospective genotyping will lead to patients being prescribed drugs which are both safer and more effective .”

AstraZeneca (2000)

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


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, PhDP4Mi Chairman and ISB president


P4 Medicine

•4P?!•Personalized•Preventive•Predictive•Participatory

20

Genetic Screening/Testing

Personalized Medicine- DH- May 2015

phenylketonuria

congenital hypothyroidism

Down Syndrome

Ethical Concerns!Safety Concerns!

http://ghr.nlm.nih.gov/condition/phenylketonuria

http://ghr.nlm.nih.gov/condition/congenital-hypothyroidism


• NOW the available diagnostic technologies

detect a single biomarker or variant in a single gene,

advances in analytical techniques

whole genome sequencing technologies

Genetic Screening/Testing


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

CYP2C9VKORC1CYP4F2APOECALU


Alleles and Egyptian Population• Warfarin Dosing


• VKORC1 (1173C>T) contributes to the 20.5% of warfarin dose variability.

• the warfarin algorithm developed by Egyptian 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)

Alleles and Egyptian Population


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

http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm

http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm


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


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


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 PharmacyUniversity of Minnesota

March 2014http://www.pharmacy.umn.edu/news/publications/record_summer13/newcurriculum/index.htm

http://www.pharmacy.umn.edu/news/publications/record_summer13/newcurriculum/index.htm




How can we get ready?Run continuing educational sessions to cover the following points

Pharmacy Today. 2008(Feb);14(2):55–66.


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.

https://class.coursera.org/genomicmedicine-001/

http://www.ncbi.nlm.nih.gov/pubmed/23839801







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