Published online: 15 July 2005; |
doi:10.1038/news050711-16
Muscular dystrophy sufferers get potential drug
lifeline
Michael
Hopkin
Molecular 'sticking
plaster' could patch up weak hearts.
|
Untreated heart muscle cells tear
after too much stretching (left), while treated ones
stay strong (right). ©
Soichiro Yasuda, U-M Medical
School | | Sufferers of muscular dystrophy may soon
be able to protect their hearts with a chemical that acts as
'sticking plaster' for muscle cells. The drug could help avoid the
heart problems that many with the condition suffer from.
Heart
failures are the second most common cause of death among patients of
Duchenne muscular dystrophy, an inherited disease. The condition's
main symptoms involve deterioration of muscles used for movement,
but the heart is often also affected, leading many sufferers to die
in their twenties.
The muscle wasting is caused by the lack
of a protein called dystrophin, although researchers did not know
why this weakens heart muscle cells. The answer seems to be that
cells lacking this protein are less resistant to stretching, say
Joseph Metzger of the University of Michigan in Ann Arbor, and his
colleagues.
Under strain
Metzger and his colleagues took
individual heart muscle cells from healthy mice and from mice
genetically engineered to lack dystrophin, and stretched the cells
by 20%. Cells lacking dystrophin were more likely to break, the
researchers report in a study published online by
Nature1.
This is because the cell membranes become torn as they are
stretched. Calcium ions, which are crucial to muscle-cell
contraction, flood in through the holes, causing the cell to
hypercontract. "The cell rolls into a little ball and dies," says
Metzger.
When the researchers treated the cells with a chemical
called poloxamer 188, a drug used to plug holes in membranes, cell
death was averted. The chemical acts like a 'finger in a dike',
Metzger's team reports, by preventing calcium influx.
Wonder
drug
All the dystrophin-lacking mice given drugs that stress the
heart by causing it to beat faster were also saved from death when
treated with poloxamer 188, the researchers add. "During the stress
test, 40% of untreated muscular dystrophy mice progressed to cardiac
failure," says Metzger's colleague DeWayne Townsend. "The poloxamer
had an instant corrective effect, which surprised us."
The
researchers warn, however, that it will be a long time before the
drug can be declared safe to use on humans. Poloxamer 188 has been
used to treat sickle-cell anaemia, but in short bursts; muscular
dystrophy patients might have to take the drug for life.
"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," Metzger
says. He and his team also want to test the drug on mice with other
types of muscular dystrophy. The Duchenne form is one of nine
different versions that affect humans.
References
- Yasuda S., et al. Nature,
doi:10.1038/nature03844
(2005).
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