Month after month, the breathlessness becomes more present, and the effort necessary to climb a few steps or walk the dog gradually becomes out of reach. Patients with chronic obstructive pulmonary disease (COPD) suffocate in their mucus, which they produce in too large a quantity … and which is particularly thick. Researchers in Australia have looked into this and discovered why their mucus is so viscous, paving the way for potential treatment for this currently incurable disease. These works are published in Nature Communications.
Shamrock proteins suspected of thickening mucus
The cells of the respiratory mucosa produce mucus continuously, to form a protective layer. This mucus is mainly made up of very long proteins, mucins, coated with glycans – a type of sugar molecule. But it also contains a small amount of TFF, proteins that form curls, much like a clover. ” TFF has long been known to make mucus more viscous (thicker), and it has been postulated that this thickening occurs in respiratory diseases. However, so far we have not fully understood how TFFs achieve this.“, Explains Professor Ethan Goddard-Borger, who directed this work. Because to prove that the excess TFFs indeed cause the increased viscosity of the mucus of the patients, it would be necessary to be able to inactivate the action of it in a specific way. If this inactivation returns its fluidity to the mucus, then the proof is made that TFF is indeed the cause of these thick secretions. ” The correlation therefore exists, but the cause remains to be proven, simply because no antagonist or mechanism of action was known before our work, so it was impossible to verify this hypothesis“, Explains Professor Goddard-Borger to Sciences and Future.
TFF “clover protein” clings to mucins
This is the step that the Australian team has successfully taken. They showed that ” TFF ‘staple’ mucin filaments by binding to their glycans“, Specifies Professor Goddard-Borger. It now remains to be proven that these connections are indeed at the origin of the unusual viscosity of the mucus of patients with COPD. If this is the case, then increasing the amount of TFF in their mucus will be a priority target to relieve them. We know that ” COPD patients produce more mucus and much more TFF than normal ”, explains Professor Goddard-Borger. In general, tissue inflammation increases the production of TFF. “This is probably part of an innate response to protect the epithelium with a thicker layer of mucus than usual when damaged or attacked by pathogens“, He specifies.
HELICOBACTER PYLORI. Interesting detail: the researchers noticed that the bacteria Helicobacter Pylori, causing ulcers in particular, also had glycans almost identical to those of our mucins. However, gastric mucus is the only one to be rich in TFF to which they can therefore cling. ” We assume that bacteria have developed this mechanism to help them colonize gastric mucus“, Concludes Professor Goddard-Borger.
If this bond causes thickening of the mucus, breaking it should thin it
Australian researchers did not stop there. After identifying the link between mucin and TFF, they also developed tools to prevent it. Next step in their work: proving that ” TFF antagonists may improve mucus clearance and lung function in preclinical models (animals, editor’s note) COPD“, Announces Professor Goddard-Borger. If it works, it could lead to the development of new therapies for COPD. ” This would not reverse the progression of the disease, but could help maintain or improve lung function to improve quality and life expectancy“, He anticipates. ” This approach could also be useful for the treatment of certain types of asthma, cystic fibrosis, idiopathic pulmonary fibrosis (rare and fatal disease, note) and dilation of the bronchi.”
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