Unpicking cause of sticky mucus

A new way to unclog the sticky mucus from the lungs of sufferers of chest disease and cystic fibrosis has been discovered by US scientists.

Cystic fibrosis affects about one person in 2500. Sufferers are prone to recurrent chest infections because the mucus they produce is thick and sticky and cannot be cleared easily from the lungs, allowing bugs to loiter and damage the lung tissue.

Doctors had assumed that the thick web-like consistency is owing to a defect in a pore or ion channel in lung cells that controls salt levels in the mucus. This alters the water content, thickening the mucus.

Now, writing in Science Translational Medicine, scientists have shown that this is only part of the story. In fact, another factor is at work and, by understanding it, University of California San Francisco (UCSF) scientist John Fahy and his colleagues have also developed a new way to clear the sticky mucus from the lungs of CF and chest-disease victims.

Mucus is rich in a gelatinous protein called mucin. Studying it under the microscope, the UCSF team found that, in the presence of the oxidising conditions produced by inflammation of the sort encountered in an infected lung, adjacent strands of mucin proteins become chemically cross-linked together. This has the effect of doubling the elasticity of the mucus, accounting for its thickened, sticky consistency.

Because the cross-links occurred between sulphur-rich parts of the mucin protein, the team developed a sulphur-containing anti-oxidant sugar called TDG (methyl 6-thio-6-deoxy-alpha-D-galactopyranoside) to reverse the effect. In tests, this was effective at breaking down and reducing the stickiness of thickened mucus by half.

Previously, doctors have tried using this sort of anti-oxidant strategy including testing the chemical NAC - N-acetyl-cysteine - but this tends to produce side effects and is unpalatable for patients.

In the present study, the new TDG compound worked twice as quickly and twice as effectively at lower doses than NAC. Furthermore, tests on mice, which received nasal doses of TDG for 5 days, showed no negative side effects, suggesting that the agent is well-tolerated in-vivo.