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Genomics
is
the study of the sequence, function and interactions of
genes. is
the study of the genome (DNA) and its products (RNA and
proteins) as it relates to an
individual's response to medicines. Pharmacogenomic research
at GSK includes several major areas of focus:
- Identifying
targets
The genes for new targets can be identified by using
DNA sequence information from resources such as the
Human Genome
Project. By comparing the sequences (order of DNA base
pairs) in newly identified genes with those of genes
whose functions are already known, scientists can make
educated
guesses about which genes might be related to specific
biochemical pathways in the body and how they might
affect the occurrence or treatment of disease. In some
cases,
it will be possible to use this information to develop
new medicines that alter specific proteins and pathways,
resulting in treatment aimed at the root cause of a
disease, not just its symptoms.
- Finding genes that vary
between healthy people and those
who have a specific disease
When a genetic difference is discovered, scientists
can use genomic tools to discover the function of
the disease-linked
gene or genes. The protein produced by the gene may
not be a suitable target itself, but may point scientists
in the right direction of finding related proteins
and
genes
that are good targets. This is another approach to
discovering new medicines.
- Screening compounds for their
likelihood of causing
some serious side effects before they are tested in humans
We know of many common variations in genes that affect
the breakdown (metabolism) of medicines, and these
polymorphisms vary among ethnic groups. People who carry
one of these
gene variants may need a higher or lower dose of a
certain drug for it to be effective or to avoid serious
side
effects - or they may need to avoid it entirely.
Predicting
the likelihood of such problems may increase the safety
and efficiency of drug development - drugs
that are likely to cause problems may be identified
earlier in the process, before they even reach the
human testing
stage. This should help protect patients and decrease
the
overall cost of drug development.
Genetics
Pharmacogenetics is
the study of how hereditary factors affect
people's responses to medicines.
Researchers predict that health care providers soon will
be able to predict a patient's response to a medicine by
examining specific portions of their .
- Determining medicine
response
GSK is incorporating pharmacogenetic research into selected
clinical drug trials – after in-depth scientific
and medical evaluation - in order to correlate patients'
genotypes with their responses to medicines. Evaluation
of DNA samples, along with analysis of data regarding
drug safety and efficacy, may make it possible to correlate
patient response to a medicine with specific genetic
markers
(such as SNPs) or patterns (haplotypes). The results
of this research are likely to affect certain patient
subpopulations
in the near future.
SNP analysis remains an expensive
effort, and GSK is working with other biotech companies
to find faster and
more cost-effective
tools for doing it, as well as developing its own in-house
technologies.
- Finding susceptibility genes
A susceptibility gene indicates a risk for developing
a disease. The gene may affect the onset and severity
of
the disease or offer protection against developing
the disease. It is not necessary or sufficient
to cause the
disease by itself, however. The discovery of susceptibility
genes enhances the understanding of a particular disease.
GSK researchers, along with scientists worldwide, are
focusing on identifying these genes and their functions.
They believe these discoveries eventually will lead
to more precise diagnoses and better treatments.
GSK
is unique among pharmaceutical companies in that it
works closely with clinical and academic groups to identify
families in which certain diseases are prevalent. The company
collects and studies medical histories and DNA samples
from family members who have the disease and those who
don't. Careful genetic analysis of these samples may help
researchers identify genes or patterns of genes (haplotypes)
that differ among affected and unaffected family members
and that may be associated with the disease.
These and other collaborations have already helped GSK
researchers identify likely susceptibility genes for psoriasis,
migraine, one type of diabetes, Alzheimer disease, and
Parkinson's disease. These breakthroughs may lead to the
identification of new targets for more effective drug therapy
that treats the underlying cause of the disease. It will
probably be seven to twelve years until the results of
this complex research begin to have a direct impact on
patients in the form of new, approved medicines.
The potential
benefits to patients of the results of these research
programs will be tremendous. In the future, it
is expected that your doctor will be able to better identify
which medicines will work best for you, and newly discovered
medicines will be more effective in treating the root
cause of your condition. Doctors will have a better understanding
of why and how chronic diseases occur and may even have
better tools for preventing them.
Bioinformatics
Bioinformatics is the study of biological systems through
the collection, sharing, and analysis of data derived from
DNA, RNA, protein, and cellular processes. It combines
the most recent work in biology, genetics, statistics,
and computer science to provide the foundation for all
aspects of genetic and genomic research at GSK. Without
these constantly evolving data processing systems, the
collection and analysis of the huge amount of data generated
in genetic research would be too time-consuming, complex
and expensive to undertake.
Bioinformatics is a major factor
in our ability to make sense of the results of the Human
Genome Project and begin
to understand the meaning of the messages contained in
the genetic code. It plays a key role in GSK's search
for susceptibility genes; for genes and proteins directly
related
to medicine response; for SNPs and SNP patterns that
can be used to predict patient response to medicines; for
identifying
tractable targets; and for defining the function of genes
and the proteins they produce. The Bioinformatics team
at GSK is a leader in applying bioinformatic tools to
drug discovery and development through pharmacogenetic
and pharmacogenomic
research.
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