I-1c gene therapy: Not such a good idea in heart failure?

January 12, 2010

Several lines of evidence, including the observation that the protein I-1 is downregulated in human failing hearts, have led to the suggestion that gene therapy to express a constitutively active form of the protein (I-1c) might provide a new approach to treating heart failure.

However, Ali El-Armouche, Thomas Eschenhagen, and colleagues, at University Medical Center Hamburg-Eppendorf, Germany, have now generated data in mice indicating that I-1c might have deleterious effects on the heart under certain circumstances, leading them to suggest that the benefit/risk ratio of I-1c gene therapy should be reevaluated.

In the study, I-1-deficient mice were engineered to express I-1c in (dTGI-1c mice). The hearts of young, resting dTGI-1c mice showed enhanced contractile function. However, when the mice were infused with catecholamine, a hormone released by the body in response to stress, they developed abnormal heartbeats and were susceptible to sudden death.

Furthermore, the hearts of aged dTGI-1c mice were found to spontaneously develop the characteristic features of . As heart failure tends to be a disease of the elderly, the authors suggest that their data need to be considered by those developing I-1c for the treatment of heart failure.

More information: Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging. View this article at: www.jci.org/articles/view/40545?key=6aaaec79fcaa30d87e28

Related Stories

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.