Personalized Medicine

Dr. Anum Gul

Personalized Medicine Involves Identifying:
Why We Need Personalized Medicine?

 People vary from one another in many ways:

 Many of these variations play a role in health and disease.

Why We Need Personalized Medicine?
The answer is Pharmacogenomics

Because everybody’s therapy is not your therapy

Pharmacogenomics
Benefits of Pharmacogenomics

 Better and safer drugs

It would be possible for the doctors to be able to examine a patient’s genetic

profile and recommend the best available drug therapy from the commencement
of the treatment.

Pharmacogenomics can also speed up recovery time and minimize the chances of
adverse reactions.
Benefits of Pharmacogenomics

 Determining accurate drug dosages

Current methods of drug dosages that are based on the weight and age of the
patient will be replaced in future with dosages based on a person’s genetic
profile and the time it takes to metabolize it.

The patient-specific drug therapy can also maximize the therapy’s value and
decrease the occurrence of overdose.
Benefits of Pharmacogenomics

 Advanced screening for diseases

Knowing a person’s genetic code will allow a person to make adequate lifestyle
changes at an early age so as to avoid or lessen the severity of genetic disorders.

Similarly, advance knowledge of a particular genetic disease will allow careful

monitoring, and treatments can be introduced at the most appropriate stage to avoid
further complications.
Benefits of Pharmacogenomics

 Decrease in the overall cost of health care

It has been suggested that the use of pharmacogenomics decreases the number of
failed drug trials, and the time it takes to get a drug approved.

The use of pharmacogenomics also reduces the length of time patients are on
medication, and possibly detects the disease early and accurately.
Personalized medicine takes into account individual genetic
differences

 Traditionally, doctors used:

Family history
Socioeconomic circumstances
Environmental factors

 Now:
genomic/genetic testing
proteomic profiling
metabolomic analysis (study metabolites)
Genomics

 Polymorphism – an area of DNA sequence that varies from person to person.

 “Single nucleotide polymorphism” (SNP) – a polymorphism in which a single

base in the DNA differs from the usual base at that position.

 “Copy number variant” (CNV) – a polymorphism in which the number of

repeats of a DNA sequence at a location varies from person to person.

 “Indel” – a polymorphism in which a DNA sequence is either present

(insertion) or absent (deletion) at a location, varying from person to person.
Types of Polymorphisms

GCCCACCTC
CGGGTGGAG

Single Nucleotide Polymorphism (SNP)

GCCCGCCTC
CGGGCGGAG

GCCCACCTCCTC
CGGGTGGAGGAG
Copy Number Variant (CNV)
GCC CTC
“Indel” Polymorphism
CGG GAG
Pharmacogenomics and Pharmacogenetics

Pharmacogenetics and pharmacogenomics are often used interchangeably but do

have distinct meanings.
Although either term refers to the use of genetic information to guide therapeutic
decision-making:
 Pharmacogenetics focuses on the influence of single gene on drug response.
 Pharmacogenomics takes a broader view of the influence of an individual's
entire genome on his or her response to drug therapy.
Importance !!

 Made-to-Order Drugs

 Pharmacogenomics shows how genes determine individual variability to drug

response and for pharmacists it would be easy to predict how a patient may
respond to drug, with the help of a genetic test before prescribing a drug.
Drug Response

 Same dose does not produce the same concentrations among patients due
to inter-patient differences in absorption and metabolism.

 Toxicity: Ability of a drug to make a person sick.

 Genetic variations have influence on efficacy and toxicity of drugs.

Drugs Effects on Variants

… and harmful to some

SNPs – A Major Source of Variation

 Single Nucleotide Polymorphisms (SNPs)

Single base change in DNA
AAGCCTA
AAGCTTA
SNPs arise as a consequence of mistakes during normal DNA
replication
Average frequency 1/1000bp
 Other sources of variation
Insertions, deletions, translocation, duplications, copy number
variation
Genome-Wide Association Study (GWAS)

 In order for physicians to know if a mutation is connected to a certain disease,

researchers often do a study called a “genome-wide association study” (GWAS).

 A GWAS study will look at one disease, and then sequence the genome of many
patients with that particular disease to look for shared mutations in the genome.

 Mutations that are determined to be related to a disease by a GWAS study can

then be used to diagnose that disease in future patients, by looking at their
genome sequence to find that same mutation.
Genome-Wide Association Study (GWAS)

 The first successful GWAS published in 2002 studied myocardial infarction.

 This study design was then implemented in the landmark GWA 2005 study
investigating patients with age-related macular degeneration (ARMD).

 It found two different mutations, each containing only a variation in only one
nucleotide (called single nucleotide polymorphisms, or SNPs), which were
associated with ARMD.

 GWAS studies like this have been very successful in identifying common genetic
variations associated with diseases.
Current Application of Pharmacogenomics

 The cytochrome P450 (CYP) is an enzyme present in the liver, which is

responsible for metabolizing more than 30 different classes of drugs.

 DNA variations in genes that code for these enzymes can affect their capability
to metabolize certain drugs.

 It has been reported that inactive forms of CYP enzymes are unable to break
down the drugs and also efficiently eliminate drugs from the body can cause
drug overdose in patients.
Current Application of Pharmacogenomics
Current Application of Pharmacogenomics

 Today, clinical trial researchers use genetic tests for identifying variations in
cytochrome P450 genes to screen and monitor patients.

 In addition, many pharmaceutical companies screen their chemical compounds

to see how well they are metabolized by variant forms of CYP enzymes.

 Enzyme called TPMT (thiopurine methyl-transferase) that plays a vital role in

the treatment of common childhood leukemia by metabolizing a class of
therapeutic compounds called thiopurines.
Current Application of Pharmacogenomics

 A small fraction of the Caucasian population have genetic variants that prevent
them from producing an active form of this protein.

 As a consequence, thiopurines rise to toxic levels in the patient because the

inactive form of TMPT is unable to break down the drug.

 Today, physicians can use a genetic test to screen patients for this deficiency, and
the TMPT action is checked to determine appropriate thiopurine dosage levels.
 Essential Factors that Play Significant Role in Making
Personalized Medicine Fully Beneficial

These factors are the following:

 Medical report for each patient must be available.
 Full genomic data for each individual involved in the clinical research must be
available.
 All the electronic tools that support physicians in taking the correct decision must
be freely accessible.
 A specific and suitable health plan must be available.
 All the personal clinical information must be available for clinical researcher (s).
Genetic Test Kit by Pharmigene

 It has done collaboration with over 50 hospitals across Taiwan.

 It has been reported that health care centers in Taiwan are now using
Pharmigene’s genetic test used to detect the presence of a key human leukocyte
antigen, HLA-B*1502, in individual patients being considered for treatment with
the drug carbamazepine.

 Patients who possess the allele and are treated with carbamazepine have been
linked to a higher risk of developing Stevens-Johnson Syndrome (SJS) and Toxic
epidermal necrolysis (TENS).
Genetic Test Kit by Pharmigene

 With the help of this genetic test, physicians have several choices of prescription
drugs to treat these symptoms; nevertheless, carbamazepine has the best efficacy and
is the least expensive.

 Moreover, the use of the companion diagnostics model, combining the use of genetic
test kits plus carbamazepine for the treatment of several thousand new patients, could
save over several billion dollars.
Challenges of Pharmacogenomics

 Gene variations and drug response

It has been reported that SNPs happens every 100–300 bases along 3 billion
bases in the human genome; accordingly, millions of SNPs must be identified
and analyzed to determine their connection with drug response.

 Limited drug options

Only one or two approved drugs are currently available for the treatment of a
particular disease condition. Moreover, if patients have genetic variations that
prevent them using these drugs, they may be left without any treatment.
Challenges of Pharmacogenomics

 Disincentives for drug companies

Most pharmaceutical companies have been successful with their one-size-fits-all

approach to drug development.

Subsequently, it costs hundreds of millions of dollars to bring a drug to market, and

now the question is, will these pharmaceutical or drug companies be willing to
develop customized drugs that serve only a small portion of the population?
Challenges of Pharmacogenomics

 Educating health care providers

Another issue with regard to patient-tailored drug is that the company needs to
introduce multiple pharmacogenomics products to treat the same condition for
different population subsets and that would certainly complicate the process of
prescribing and dispensing drugs in the clinics and hospitals.

Additionally, doctors or physicians will have to take an extra diagnostic step to

determine which drug is best appropriate for each patient.
Here’s My Sequence ...
The route to a new medicine … is a long one
… and an expensive one !!
In your wallet May be by 2050..