Novel gene therapy that protects ischemic myocardium in mouse model may limit myocardial loss following acute infarction
A novel gene therapy that responds specifically
to ischemic myocardial cells may eventually protect human patients
against further myocardial loss following an acute infarction, according
to an article in the April issue of Hypertension.
The American research team designed an oxygen-sensitive
biosensor that triggers expression of protective genes when myocardium
becomes ischemic and inhibits expression after adequate blood flow
has been restored. The research technique, which was tested in mice,
minimized further injury after an acute myocardial infarction.
The molecular sensor contains both a means
to increase the expression of protective heme oxygenase-1 (HO-1)
genes and an oxygen-sensitive switch that can turn off expression
after ischemic conditions ease. In the experiments, researchers
injected this molecule directly into the hearts of mice one hour
after the mice had an acute myocardial infarction.
Ten days following their infarctions, mice
that received the biosensor-regulated gene therapy showed less myocardial
scarring and better recovery of ventricular function than control
mice injected with saline only. The researchers demonstrated with
molecular techniques that turning on expression of the protective
HO-1 genes prevented further myocardial cell infarction, limiting
the area of damage.
Two of the researchers, M. Ian Phillips,
PhD, DSc and Yao Liang Tang, MD, envision administering such therapy
to patients after a first myocardial infarction to limit damage
and prevent future infarctions. While much work remains to test
and refine such a therapy, Phillips said that the new concept might
eventually be an alternative to stents and bypass surgery.
“Repeated bouts of myocardial ischemia cause
cumulative tissue damage in the heart vessels that can lead to a
fatal heart attack,” said Phillips. “Therefore, what patients need
is a gene therapy strategy that acts in the heart and switches on
or off, so that the therapeutic protein is produced only where and
when it is needed.”
“One of the exciting aspects of the approach,
described by Tang et al, is the ability to directly link expression
of potentially therapeutic genes to a pathological stimulus associated
with myocardial infarction, ischemia,” stated an editorial in Hypertension.
“Ultimately, this area of research will pave the way for development
of ‘smart’ therapies for the heart that allow for early and rapid
treatment of a wide variety of cardiac ailments.”
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