Biomedical Engineering Reference
In-Depth Information
left ventricular remodeling in the Corgentin-treated group, compared to placebo.
Postmortem analysis of the hearts provided convincing histological evidence of the
potential for post-infarct myocardial protection with this therapy. The initial clinical
studies for Corgentin will be designed in an attempt to secure product registration
for use in patients with acute ST-elevation myocardial infarction undergoing percu-
taneous coronary intervention with or without associated fibrinolysis.
Congestive Heart Failure
Although advances in medical treatments have dramatically reduced the overall
mortality rate due to heart disease, death due to CHF continues to rise. The present
treatments for the loss or failure of cardiovascular function include organ transplan-
tation, surgical reconstruction, mechanical or synthetic devices, or the administra-
tion of metabolic products. Although routinely used, these treatments are not without
constraints and complications. Ideal and effective therapy, particularly for end-stage
CHF, has been elusive. The varied causes of heart failure include abnormalities of
ion handling, cellular signaling, neurohormonal control, and apoptosis, all of which
are potentially amenable to genetic manipulation.
Rationale of Gene Therapy in CHF
The central clinical problem in CHF is a lack of therapies to target the underlying
molecular defects that lead to chronic ventricular dysfunction. Gene therapy holds the
promise of retarding the progression, preventing, and perhaps reversing heart failure.
Substantial evidence points to a final common pathway in failing myocardium,
including distinct changes in intracellular. Alterations in intracellular calcium signaling
play a crucial role in the pathophysiology of heart failure, and in recent years, somatic
gene transfer has been identified as an important tool to help understand the relative
contribution of specific calcium-handling proteins in heart failure.
An attractive strategy to address these alterations is cardiac gene therapy and
several distinct approaches have been undertaken during the last decade with
impressing therapeutic benefit, at least in animal CHF models. The present focus
of research is the clinical translation of cardiac gene therapy including the optimi-
zation of vectors, delivery strategies, and testing the compatibility with established
pharmacologic treatment to improve the prognosis of CHF in the near future
(Pleger et al.
2007
).
b-ARKct Gene Therapy
The upregulation of GPCR kinase 2 (GRK2) in failing myocardium appears to
contribute to dysfunctional beta-adrenergic receptor (b-AR) signaling and cardiac
function. The peptide b-ARKct, which can inhibit the activation of GRK2 and
improve b-AR signaling, has been shown in transgenic models and short-term gene
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