| Background
Approximately 60 million people have
cardiovascular disease in the United States. Genetic polymorphisms are
identified among the factors involved in the pathophysiology of
cardiovascular disease. Safe and effective drugs for treatment of
cardiovascular disease are needed and the emerging understanding of the
human genome is stimulating researchers to assign top priority to
identification of key genetic targets in developing new drug
therapies.
Current research focus is on identification of specific targets in
genetic/molecular pathways/systems. Therapeutic interventions will be
developed as a result of this research and it will become the basis
of significant future drug development. The goal is to
expedite testing therapeutic hypotheses in humans and develop
strategies to identify optimal therapy for individual patients. Our
challenge is to unravel and identify targets accessible to drug
intervention and select the correct pharmacologically accessible
targets.
Validation of a pharmaceutical target comes only with successful
clinical trials. Such studies can help provide evidence for the function
of the target, as well as models for drug screening and further
pharmacological research. Which targets and interventions should receive
priority for clinical investigation and what drug modality can be
used to evaluate the hypothesis in humans is the question. Polygenic
diseases will provide multiple targets for therapy, each requiring
clinical investigation. These various therapeutic intervention strategies
would identify targets that are not treatable by drugs today.
The effect of human genetic variance on responses to therapy will
influence drug development, clinical trials and clinical
practice. DNA, now routinely obtained in many clinical trials, will
be examined retrospectively for association of genetic variance with
outcomes. Biomarker panels for disease will provide strategies to
diagnose, monitor, and predict outcomes of various therapies. New
treatments will only develop if these approaches are integrated into the
drug discovery process from hypothesis to clinical evaluation.
The University of Florida is initiating a study that will develop
a biomarker database of INVEST invest.biostat.ufl.edu
patients with cardiovascular disease. By collecting genetic samples
and pairing them with clinical information already collected in
INVEST, specific hypotheses can be tested on the relationship between
genetics and specific clinical outcomes. We will test the relationships
between genetic polymorphisms related to cardiovascular disease, drug
response and survival, morbidity, and treatment response. Future
studies using the genetics database may include studies of the role of
other genetic polymorphisms in the development and outcome of various
cardiovascular diseases. References |
