For the benefit of patients with respiratory diseases!

Asthma, chronic pulmonary obstruction, cystic fibrosis, and lung cancer, many lung diseases affect hundreds of millions of people around the world

The good news is that, according to a research paper recently published in the top academic journal Nature, scientists have now finally developed a drug that specifically blocks the excessive secretion of mucus in the airways, promising to improve the lives of patients whose airways are blocked by mucus

For healthy people, mucus is 97% water, with only a small amount of mucin

But in diseases such as obstructive pneumonia, a persistent inflammatory state stimulates mucin hypersecretion

In their work over the past two decades, scientists studying the mechanism of mucin secretion have discovered an unexpected "coincidence" from neuroscientists: the lungs and the brain share similar secretion mechanisms

Simply put, nerve cells release neurotransmitters at the synapse, and after receiving calcium signals, they stimulate a structure called "vesicle" through key molecules such as synaptotagmin to fuse with the cell membrane.

"We figured out the secretory mechanism, all the major players," said Professor Dickey

▲ The secretion of mucin by airway epithelial cells involves the mechanism of fusion of vesicles with cell membranes under the stimulation of calcium signals.

In this study, multi-institutional collaborative work validated Syt2 as a viable therapeutic target using different preclinical models

Based on this mechanism, the research team designed a polypeptide SP9 that can bind to Syt2 to prevent the protein complex with which Syt2 cooperates from responding to calcium signals

Dr.

▲The interaction of synaptotagmin (orange) with protein complexes (shown in blue, red, and green) necessary for synaptic fusion with the engineered peptide SP9 (shown in bright yellow) was used to inhibit the secretion of mucin (Image source: Reference [3]; Illustration: Eric D.

Next, the research team further modified SP9 by binding it to another peptide PEN that can penetrate the cell membrane, helping SP9 successfully enter the secretory cells to play a role

Subsequently, the research team developed PEN-SP9 as a nebulizer, and confirmed in mouse experiments that this drug can help animals avoid excessive mucus blocking the airway and does not affect the normal secretion of mucin

One of the leaders of the study, Professor Axel Brunger of Stanford University, said that they will also continue to optimize SP9, hoping to enter clinical trials in the next few years to benefit patients as soon as possible

References:

[1] Ying Lai et al.

[2] Irina Gitlin & John V.
Fahy (2022) Mucus secretion blocked at its source in the lungs.
Nature.
Doi: https://doi.
org/10.
1038/d41586-022-00700-8

[3] Novel therapy could help people with asthma, COPD, cystic fibrosis and cancer-related lung disease.
Retrieved Mar.
29, 2022 from https:// Scientists develop compound that could treat asthma, other mucus-induced lung diseases.
Retrieved Mar.
29, 2022 from https://med.
stanford.
edu/news/all-news/2022/03/excessive-mucus-secretion -blocking-compound.
html