Science News
from research organizations

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

Date:
January 11, 2010
Source:
Journal of Clinical Investigation
Summary:
Several lines of evidence have led to the suggestion that gene therapy to express a constitutively active form of the protein I-1 (I-1c) might provide a new approach to treating heart failure. However, researchers have now generated data in mice that indicate 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.
Share:
       
FULL STORY

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 heart muscle cells (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 heart failure.

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 gene therapy for the treatment of heart failure.


Story Source:

The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal References:

  1. Katrin Wittköpper, Larissa Fabritz, Stefan Neef, Katharina R. Ort, Clemens Grefe, Bernhard Unsöld, Paulus Kirchhof, Lars S. Maier, Gerd Hasenfuss, Dobromir Dobrev, Thomas Eschenhagen and Ali El-Armouche. Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI40545
  2. Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging. Journal of Clinical Investigation, January 10, 2010

Cite This Page:

Journal of Clinical Investigation. "I-1c gene therapy: Not such a good idea in heart failure?." ScienceDaily. ScienceDaily, 11 January 2010. <www.sciencedaily.com/releases/2010/01/100111171842.htm>.
Journal of Clinical Investigation. (2010, January 11). I-1c gene therapy: Not such a good idea in heart failure?. ScienceDaily. Retrieved July 7, 2015 from www.sciencedaily.com/releases/2010/01/100111171842.htm
Journal of Clinical Investigation. "I-1c gene therapy: Not such a good idea in heart failure?." ScienceDaily. www.sciencedaily.com/releases/2010/01/100111171842.htm (accessed July 7, 2015).

Share This Page: