Muscular dystrophy sufferers get potential drug lifeline
Molecular 'sticking plaster' could patch up weak hearts.
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.
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.
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.
- Yasuda S., et al. Nature, doi:10.1038/nature03844 (2005).