| Autor: |
Kassandra S. Thomson, PhD, Guy L. Odom, PhD, Charles E. Murry, MD, PhD, Gregory G. Mahairas, PhD, Farid Moussavi-Harami, MD, Sam L. Teichman, MD, Xiaolan Chen, PhD, Stephen D. Hauschka, PhD, Jeffrey S. Chamberlain, PhD, Michael Regnier, PhD |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
JACC: Basic to Translational Science, Vol 1, Iss 7, Pp 666-679 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2452-302X |
| DOI: |
10.1016/j.jacbts.2016.07.006 |
| Popis: |
Despite recent advances, chronic heart failure remains a significant and growing unmet medical need, reaching epidemic proportions carrying substantial morbidity, mortality, and costs. A safe and convenient therapeutic agent that produces sustained inotropic effects could ameliorate symptoms and improve functional capacity and quality of life. The authors discovered that small amounts of 2-deoxy-ATP (dATP) activate cardiac myosin leading to enhanced contractility in normal and failing heart muscle. Cardiac myosin activation triggers faster myosin cross-bridge cycling with greater force generation during each contraction. They describe the rationale and results of a translational medicine effort to increase dATP levels using a gene therapy strategy that up-regulates ribonucleotide reductase, the rate-limiting enzyme for dATP synthesis, selectively in cardiomyocytes. In small and large animal models of heart failure, a single dose of this gene therapy has led to sustained inotropic effects with no toxicity or safety concerns identified to date. Further animal studies are being conducted with the goal of testing this agent in patients with heart failure. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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