PERSONALIZED MEDICINE

Guide:

Presented by,

Dr. Seema Nair P.

Midhun J. Singh
M.Tech Molecular Medicine

CONTENTS

Introduction What is Personalized Medicine..?? Core elements of PGM Variations among Human Pathways in developing Personalized Medicine Role of SNPs, Biomarkers Pharmacogenomics An example.. The Challenges The Promise Of Personalized Medicine Conclusion References

INTRODUCTION

Humans are unique individuals- true of our genomes as well. There are small differences in our DNA that are unique. The natural variations (DNA polymorphisms) found in our genes play a role in our risk of getting or not getting certain diseases. In current therapeutics world, a drug doesnt work for all the patients for all the time.

INTRODUCTION

Advances in human genome research- opening a new paradigm for practicing medicine. Personalized medicine provide the link between an individuals molecular and clinical profiles. Allow physicians to make the right patient-care decisions. Patients get the opportunity to make informed and directed lifestyle decisions for their future wellbeing.

WHAT IS PERSONALIZED MEDICINE..??

The tailoring of medical treatment to the individual characteristics of each patient. It is not the creation of drugs or medical devices that are unique to a patient. Individuals classified into subpopulations that differ in their susceptibility to a particular disease or response to a specific treatment. This could avoid a trial-and-error approach to prescribing.

the right treatment for the right person at the right time.

WHAT IS PERSONALIZED MEDICINE..??

Current Practice Personalized Medicine

Trial and Error

Right treatment for the right person at the right time

CORE ELEMENTS OF PGM

Molecular Medicine o Pharmacogenomics o Health information technology
o


Personalized medicine is being advanced through data and technologies from Human Genome Project Genome Wide Association Studies (GWAS) DNA sequencing

PATHWAYS IN DEVELOPING PERSONALIZED MEDICINE

MILESTONES IN PERSONALIZED MEDICINE

Year 1953 Landmarks Identification of the double-stranded structure of the DNA The genetic code is cracked, revealing how DNA sequences code for protein. Gene sequencing techniques invented. A polymerase chain reaction technique is invented for in vitro amplification of DNA sequences. The Human Genome Project launched. Herceptin, a drug that works on a 25 percent subpopulation of breast cancer patients, approved by the U.S. Food and Drug Administration (FDA).

1967

1975 1983

1990 1998

CONTD.
Year 19902000 Landmarks The genomic decade. Sequencing of the human genome. Application of genomic technologies to drug development: pharmacogenomics. Cell and gene therapies. The sequencing of the human genome declared. complete after 13 years and a $3 billion investment. US Senator Obama (now President) introduced Personalized MedicineAct. Genetic Information Nondiscrimination Act passed in the USA. Post-genomic decade. Development of personalized medicine and integration of diagnosis with therapy in healthcare.

2003 2006 2008 20012010

MAJOR DRUGS INEFFECTIVE FOR MANY

Genetic factors may account for 20-95% of this variation

ROLE OF SNPS

SNPs make up about 90% of all human genetic variation. Two of every three SNPs involve the replacement of cytosine (C) with thymine (T). SNPs can occur in both coding (exons) and non-coding (introns) regions of the genome. Many SNPs have no effect on cell function Certain others could predispose people to disease or influence their response to a drug.

A SNP in a drug metabolism enzyme - a poor clinical outcome by causing variability in drug response A SNP in a drug target -change the pharmacodynamics of drug response.

ROLE OF BIOMARKERS

Biomarker A molecule that indicates an alteration in physiology from the normal. Biomarkers will enable early diagnosis of disease to facilitate optimization of therapy. play an important role in combining diagnosis with therapeutics an important feature of personalized medicine. Can be used as drug targets in drug development. The importance of biomarkers in treatment selection and patient management is anticipated to increase in the coming years

AN EXAMPLEIN BREAST CANCER

(HER-2) protein on the surface of breast cancer cells is over expressed in approximately 2530% of breast cancer patients. Herceptin, was one of the first drugs to leverage the power of genetics to treat disease. Prescribed only for patients whose genetic tests reveal an over-expression of the protein HER2

AN EXAMPLEIN BREAST CANCER

Herceptin is customized to target only those cells associated with disease. Studies show that this targeted approach Risk of death reduced by 33 percent Risk of recurrence reduced by 52 percent Global herceptin sales were of the order of US $276 million in the year 2000

AN EXAMPLEIN HIV/AIDS
Selzentry (maraviroc) is a personalized medicine targeted for the treatment of a specific strain of HIV known as CCR5-tropic. Developed in conjunction with the Trofile assay

Identify which patients will benefit from this drug choosing the best treatment options for patients who may be resistant to or intolerant of other available therapies.

AN EXAMPLEIN CARDIOVASCULAR DISEASE

Drug Coumadin (warfarin), most commonly used to prevent blood clots Dosing adjusted through multiple rounds of trial and error Hemorrhage (bleeding) is the major common side effect of warfarin. Three SNPs, in two genes cytochrome P450, CYP2C9, and VKORC1 contribute significantly to the variability among patients in dose requirements.

CYP2C9*2 reduces warfarin metabolism by 30%, and CYP2C9*3 reduces warfarin metabolism by 90%. The genetic test identifies individuals who metabolize warfarin more slowly than normal -predetermine the right dose for a patient the first time. integrating genetic testing would avoid 85,000 serious bleeding events & 17,000 strokes annually.

PM AND INDIA

The concept of personalized therapy based on individual variations has existed since centuries through the practice of Ayurveda. Indian Genome Variation (IGV) Consortium


Aims to provide data on validated SNPs in over a thousand genes in 15,000 individuals drawn from Indian subpopulations

The important genetic information from this project facilitate research on -disease predisposition -adverse drug reactions -population migration.

ECONOMICS OF PERSONALIZED MEDICINE

Increase in the treatment efficacy of personalized treatment is difficult to measure in financial terms. There are over 1,200 genetic tests available, mostly for diagnosis of diseases


the cost varies from $150 to over $1,000

Initial cost of testing may be high, PM will reduce healthcare costs by

eliminating the wasteful use of ineffective drugs  reduce the cost of care for adverse effects of drugs.


ECONOMICS OF PERSONALIZED MEDICINE

It typically costs a drug company about $800 million to develop, test, and bring to market a single drug. The cost for pharmacogenomics-based clinical trials would be less than that of conventional clinical trials because fewer patients would be required for such trials.

THE CHALLENGES
Diseases, like diabetes, hypertension etc. are polygenic Multiple genetic variables also determine how medicines are metabolized by the body. Personalizing medicine -more than peoples genes Patients are not familiar with personalized medicine. Three out of four patients have not heard of personalized medicine. Ethical and Regulatory Aspects

THE PROMISE OF PERSONALIZED MEDICINE

Introduction of new technologies would reduce the cost of personalized genome analysis to under $1000

A future with more compliance and far less side effects. It results in providing benefits without toxicity.

the current ineffectiveness rate of medicines range from 40 to 75 % -percentage will dramatically decrease with the venue of personalized medicine.

CONCLUSION

Using pharmacogenomic strategies with family and clinical histories offer an exciting and promising advancement towards personalized medicine. PM is financially feasible, as it will reduce the costs of drug development by shortening the drug development cycle PM has potential to improve efficacy of drug therapy and reduce incidence of ADRs.

REFERENCES

Bill Snyder (2010) The Possibilities of Personalized Medicine, Vanderbilt Medicine, Volume 27, Number 1:13-18 Nupur Mehrotra and Rajeev Soni (2005) Pharmacogenomics: A Step Towards Personalized Medicine, Bioinformatics India Journal, Vol-III, Issue-IV: 11-17 Suraksha Agrawal and Faisal Khan (2007) Human genetic variation and personalized medicine, Indian J Physiol Pharmacol 2007; 51 (1) : 728 Geoffrey S. Ginsburg and Jeanette J. McCarthy (2001) Personalized medicine: revolutionizing drug discovery and patient care, TRENDS in Biotechnology Vol.19 No.12 December :491-497 Panga Jaipal Reddy et al.,(2011) Personalized Medicine in the Age of Pharmacoproteomics: A Close up on India and Need for Social Science Engagement for Responsible Innovation in Post-Proteomic Biology, Current Pharmacogenomics and Personalized Medicine Vol.9, 159-167

REFERENCES

Kewal K. Jain, Textbook of Personalized Medicine, Springer 2009 Sean Xinghua Hu, Thomas Foster, and Ann Kieffaber (2005) Pharmacogenomics and personalized medicine: mapping of future value creation, BioTechniques Vol. 39, No. 4:113-121 Rost S., Fregin A. (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 5;427(6974):537-541 Future of Health care and Medicine, The New Health Report(2011) [ONLINE] https://www.quintiles.com/newhealthreport Personalized Medicine: An Introduction [ONLINE] https://www.personalizedmedicinecoalition.org