The
primary focus of deCODE's business is the development of new, more
effective drugs based upon our gene discovery work in some 50 common
diseases. Our population approach and unique competence in human
genetics underpin the breadth of our drug development work, from target
discovery through clinical trials.
Our approach offers several
advantages for developing better drugs. Most medicines today are
compounds that are aimed at treating the symptoms of disease, seldom
the underlying causes. The principal reason for this is that to date
the basic biology and pathogenesis of most of the big public health
challenges - such as heart attack, stroke, Alzheimer's disease,
osteoporosis, or asthma - are poorly understood. These diseases are
common because of their complexity, and result from the interplay of
both inherited and environmental factors. Genetics offers a means of
unravelling this complexity and a window into the biology of disease.
Through the identification of key genes involved in predisposition to a
given disease, it is possible to study the proteins these encode and to
tease out the biological pathway of the disease. Drugs targeting key
elements in the pathway may be able to effectively disrupt the disease
process.
Using
our population approach and resources, we can efficiently conduct
population- and genome-wide scans to home in on the key genetic factors
involved in any common disease in a virtually hypothesis-free manner.
To date, deCODE has isolated 15 genes and drug targets in 12 common
diseases, and mapped genes in some 16 more. This is an unmatched record
of success. We have been able to do this through the analysis of
genotypic and medical data from over 100,000 volunteers in our gene
research in Iceland - more than 50% of the adult population - in tandem
with our genealogical data linking together the entire present-day
population and stretching back over 1100 years. By mining these
datasets we can effectively trace the inherited components of a given
disease, pinpointing the key disease genes as well as the specific
markers or haplotypes within these genes that correlate with the
disease.
Through functional biology research we are able to gain an understanding of the
role of the proteins encoded by the disease genes and to select optimal targets
for therapeutic intervention. Our structural biology and chemistry groups can
generate three-dimensional images of our targets and discover and develop novel
small-molecules that interact with these targets.
Our
program in DG041
offers an example of how our approach has taken us in only three years from the
identification of a disease gene and novel target and into mide stage human
clinical trials. At the same time, as we have shown in our drug development program
in
heart attack,
there are existing compounds developed by others for different
indications that we may be able to in-license and enter directly into
clinical trials, thereby leapfrogging over several years of discovery
work.
In our clinical development work we are pioneering the
application of population data to the clinical development process,
creating what we call the Information-rich Clinical Trial
TM,
or IRCT
TM.
The goal of this paradigm is to bring detailed genetic and phenotypic data to
bear on the design, recruitment and analysis of the clinical development process,
making trials much more sensitive instruments for gauging the effectiveness of
new drugs. Because we can recruit cohorts with a detailed understanding of the
pathways through which patients are susceptible to disease, the IRCT approach
enables trials that are smaller, faster and more informative than traditional
trials. We believe this offers an important means of better managing risk in
the drug development process and of maximizing the therapeutic potential of new
drugs.
