Lung mucus can be fatal to asthmatics, but scientists at the University of Colorado Anschutz Medical Campus have broken down these secretions at the molecular level, often reversing the fatal effects.
In a study published in the journal on Monday Nature CommunicationsResearchers have described how they created an inhalation therapy that interferes with the production of excess mucus by reducing disulfide bonds and opening the airways in mice. The same treatment had a similar effect on human mucus samples.
“Currently, about 10% of the population suffers from asthma,” said Dr. Christopher Evans, a professor of lung science and critical care at CU School of Medicine, the lead author of the study. “Excessive mucus blocks airflow, causes wheezing, and exacerbates the effects of inflammation and contraction of the muscles that line the airways.”
However, treatments for asthma, such as bronchodilators and steroids, are rarely effective against mucus. Evans said the mucus is hydrated to make it easier to cough, but the problem cannot be treated at the molecular level.
He and his team targeted macromolecules in mucus called macromolecular mucin glycoproteins. They help protect the lungs and respiratory tract from infection in healthy people. However, overproduction can create gelatinous plugs that block the airways, as seen in asthma and other lung conditions.
Researchers sought to stop this process by breaking mucin disulfide bonds, which contribute to mucus overproduction. They treated asthmatic mice with a chemical known as TCEP (Tris (2-carboxyethyl) phosphine). It also acted on human mucus sampled from asthma patients.
“We have shown that disruption of mucin disulfide bonds loosens mucus and reverses the pathological effects of mucus hypersecretion in a mouse allergic asthma model,” said a postdoctoral fellow at CU Anschutz, co-author of the study. Dr. AnaMaria Jaramillo said. “Loosening mucus reduces airway inflammation, enhances mucus fimbria clearance, and eliminates airway hyperactivity.”
Researchers say TCEP is likely to irritate the human lungs, but adds something similar to drugs that treat asthma, COPD, cystic fibrosis, and other lung diseases to reduce mucus. Said that it was much more effective.
“This kind of strategy can be used to develop safer mucolytic compounds,” says Evans. “They were able to help steroids and albuterol penetrate deep into the lungs and airways. They could be used as adjuvant therapy.”
These new compounds may also be used to treat COPD, pulmonary fibrosis, and infections such as pneumonia and Covid-19 that attack the lungs and airways.
“These findings establish a basis for developing treatments that reduce the effects of hypersecretion of mucus in asthma,” Evans said. “I believe they have the potential to save lives.”
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