Easy breathing

Biologists have hit upon a molecule that can prevent the airways of asthmatic mice from clogging up. The finding may help human sufferers of respiratory diseases.

More than 100 million people worldwide suffer from asthma. They experience recurrent attacks of wheezing and breathlessness as their airways narrow and secrete large amounts of mucus.

Every year some 180,000 people die from asthma, and more mucus means a higher risk of mortality, notes Kenneth Adler, who studies respiratory diseases at North Carolina State University in Raleigh. Sputum can damage the airway lining, making patients more susceptible to bacterial infection and respiratory failure.

Adler's team made a molecule, called MANS peptide, and tested it on mice that suffer from asthma-like symptoms - when the rodents are exposed to an allergen, their airways swell and mucus production rockets fivefold. A single dose of the peptide drug given 15 minutes before an induced asthma attack prevented the build-up of mucus1.

"The peptide is potentially useful in the clinic," says Joe Garcia, head of pulmonary and critical-care medicine at the Johns Hopkins University in Baltimore, Maryland. Asthmatics already use drugs that help relax the airways, but there are no medications for reducing mucus. "This would complement, not replace standard therapies," he says.

The drug may also help those with cystic fibrosis and the smokers' disease, chronic obstructive pulmonary disease, who also suffer from sputum-related breathing difficulties.

Mucus explosion

In the mouse model, the MANS peptide targets mucus-making cells found in the airway lining, but it may also affect other cell types, cautions Garcia. This could produce unwanted and as yet unknown side effects, so tests are needed to check the molecule's safety.

The treatment stops the secretion of mucus, not its production. This means that the sticky substance may build up inside cells and eventually push them to bursting point, cautions Duncan Rogers from Imperial College, London, who studies respiratory disorders. This could trigger a mass release of mucus, which could obstruct the airways.

Alternatively, because the cells are no longer secreting mucus, they may simply shrivel and disappear, counters Garcia. Longer-term studies will be needed to find out.

References

1. Singer, M. et al. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nature Medicine, doi:10.1038/nm983, (2004).