Cardiac Stretch
Chemical sealant restores heart muscle cells’ ability to lengthen in dystrophin-deficient
mice
U-M scientists have found a chemical “band-aid” that can repair
damage to cardiac muscle cells and prevent heart failure in mice with the same
genetic mutation that causes Duchenne muscular dystrophy in people.
| Without poloxamer 188 |
With poloxamer 188 |
|
Left column: This series of four images shows a cardiac muscle cell from a dystrophin-deficient mouse being stretched between microcarbon fibers. Untreated myocytes from these mice break and die after repeated 20 percent stretches.
Right column: This series of four images shows a cardiac muscle cell from a mouse that was treated with P188. Even though it has the same genetic defect, it survives 20 percent stretches without breaking.
Photo: Soichiro Yasuda, U-M Medical School |
This mutation in a gene called dystrophin causes skeletal muscle to deteriorate
and affects cardiac muscle, too. Many people with Duchenne muscular dystrophy
die in their 20s from heart failure caused by cardiomyopathy, a gradual weakening
of the heart muscle.
“Our research found that mice with the dystrophin mutation have stiffer
heart muscle cells, which don’t relax and lengthen as readily as they
do in normal mice,” says Joseph M. Metzger, Ph.D., professor of molecular
and integrative physiology and of internal medicine in the U-M Medical School.
“This makes them vulnerable to damage when they must stretch to make room
for blood flowing into the heart.”
The U-M research team found that bathing heart muscle cells from dystrophin-deficient
mice with poloxamer 188 — a chemical sealant used in manufacturing and
the pharmaceutical industry — restored the cells’ ability to stretch
without damage. And an infusion of P188 protected the mice from heart failure
during a stress test.
“If issues of dosing and long-term safety can be resolved, our research
suggests that poloxamer 188 could be a new therapeutic agent for preventing
or limiting progressive damage to the hearts of patients with muscular dystrophy,”
Metzger says.
—SFP
For an expanded version of the story:
www.med.umich.edu/opm/newspage/2005/poloxamer.htm
 
|
