Development of aerosol-type ‘fixed peptide’ that inhibits mucus production
MD Anderson Cancer Center, University of Texas, USA, thesis in ‘Nature’
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(Seoul = Yonhap News) Reporter Ki-cheon Han = Airway refers to the passageway through which air passes through the nose and into the lungs.
Usually the airways are covered with a thin mucous membrane. Mucin protein secreted into the airways absorbs moisture and forms a mucous membrane.
This mucous membrane of the airway is beneficial to health.
This is because the cilia of the airways, which have become sticky with mucus, block pathogens and dust from entering.
However, if the mucin protein is secreted explosively all at once, it leads to a dangerous ‘mucous obstructive pulmonary disease’.
Proteins that do not absorb enough water can produce thick, thick mucus that can block airways or impair lung function.
Asthma, chronic obstructive respiratory disease (COPD), and cystic fibrosis, which can be life-threatening if mishandled, all fall into this category.
Cancer patients whose immune system is compromised during treatment often become seriously ill with this type of lung disease.
Scientists at the University of Texas MD Anderson Cancer Center have developed a treatment that blocks the outrageous secretion of airways.
The results of this study conducted by Burton Dickie, a professor of respiratory medicine, were recently published as a paper in the journal Nature.
Human airway ciliary cells (red) and NS1 protein (green) infected with RS virus.
RS virus interferes with the immune response of the host cell with this protein.
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According to the outline of the paper published on the American Association for the Advancement of Science (AAAS) site (www.eurekalert.org) on the 29th, when too thick mucus blocks the airways, symptoms ranging from mild cough to severe lung disease appear.
This is why mucus is such an important issue in respiratory medicine.
It is estimated that hundreds of millions of people worldwide suffer from this type of mucinous obstructive pulmonary disease.
In the United States, it is known that there are about 25 million asthmatics and 16 million adults with COPD.
Professor Dickie, who is the co-corresponding author of the paper, said, “Most of the drugs used for these diseases relieve inflammation or widen the airways to make breathing easier for patients. said
Among the mucin proteins in mucus or saliva (saliva), there is a type that blocks transmission by enclosing virus particles.
In fact, it has been reported in academia that the new coronavirus, which is mixed with saliva and discharged, is transmitted more easily if there is no protein.
Professor Dickie’s team, who has been studying muchin protein secretion for a long time, has previously discovered a protein called synaptotagmin that plays a key role.
This protein, together with a specific SNARE complex, triggered a key ‘cell membrane fusion’ process triggered by free calcium Ca2+.
The research team pointed to the type 2 synaptotagmine (Syt2) protein as the optimal target to block muchin secretion.
Blocking the expression of this protein has been shown to prevent the abrupt secretion of many mucin proteins.
However, the gradual and rudimentary mucin secretion function required to maintain airway health was not impaired.
The research team designed a ‘hydrocarbon anchoring peptide’ named ‘SP9’ to block the expression of Syt2 protein.
This type of immobilized peptide has been used as a cancer treatment because it shows a property of tightly binding to a protein target.
SP9, developed as an inhalable aerosol, successfully disrupted Ca2+-triggered membrane fusion in a model of a reconstitution system from a research team at Stanford Medical School, a partner institution.
In addition, when SP9 combined with a cell-membrane peptide was applied to airway epithelial cells, rapid mucin secretion was suppressed.
Nuclei of ‘intrinsic lymphocytes’ (blue) wrapped in fatty acid droplets (green).
Asthma patients with severe bronchial inflammation also have an allergic reaction to a low-concentration antigen. In this case, intrinsic lymphocytes play a key role.
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Aerosol-type SP9 also showed efficacy in relieving mucin secretion and airway mucosal obstruction in a mouse model test.
If SP9 is approved as an inhaled drug, it will help to save the life of a patient whose airway is suddenly blocked due to excessive secretion of mucin protein.
The research team plans to accelerate the development process of SP9 and start clinical trials in a year or two.
Meanwhile, scientists from Stanford University of Medicine in the US and Ulm University in Germany participated in verifying the efficacy of SP9 in this study.
cheon@yna.co.kr
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