The protein that could help fight asthma

The protein that could help fight asthma
April 20, 2017

Researchers from the UNC School of Medicine may have found the first new direction for treating asthma in years. They isolated a protein that when missing from the airway causes the swelling, constriction and mucus emblematic of asthma.

Asthma InhalerMore than 24 million Americans and more than 334 million people worldwide live with asthma, making it one of the most common respiratory diseases in the world. Asthma symptoms can be life threatening for some people, so any new treatment could potentially improve or even save many lives.

Robert Tarran, a professor of medicine at UNC’s Marisco Lung Institute and co-author of the study published in the journal Nature Communications, came across a protein called SPLUNC1 when researching cystic fibrosis, another respiratory disease.

SPLUNC1, also called BPIFA1, floats between cells where mucus contacts the lining of the airway. It has the ability to regulate, through ion channels, how hydrated the airway fluid is. As such, researchers are looking to use it to soften the hard mucus of cystic fibrosis and help deliver antibiotics in upper respiratory infections.

Wondering if SPLUNC1 could possibly play a part in asthma, because of how it affects the upper respiratory tract, the researchers measured the levels of SPLUNC1 in airway samples from asthmatic and non-asthmatic volunteers and ran similar tests in mice.

In both the humans and the mice, SPLUNC1 levels were greatly depleted in asthmatic participants compared to healthy ones and mice with COPD and allergies, two respiratory illnesses that can have similar effects to asthma. The depletion of SPLUNC1 was unique to asthma.

Airway InflammationThey also found that SPLUNC1’s effects are not limited to hydrating the throat. In mice with low levels of SPLUNC1, disturbance by a small amount of allergen caused a severe reaction in the throat. That is called airway hyperresponsiveness, and is one of the hallmarks of an asthma attack. In both the mice and human cells in test tubes, lack of SPLUNC1 prevented the airway smooth muscle—the muscles that help us breathe and move mucus that we cannot consciously control—from relaxing, which constricts the airway.

Further, the researchers measured the crystal structure, or precise placement of every atom in the protein, of SPLUNC1. That structure not only tells researchers more about the protein itself, but also about the pieces of SPLUNC1 that actually do work within the airway, called active sites

The active sites, the researchers think, could be used as a potential asthma medicine. Using an inhaler or nebulizer, the synthetic versions of the active sites, the proteins themselves or a new molecule based on SPLUNC1, could enter the airway and prevent asthma symptoms. Researchers hope to study that possibility in the future.

Like the asthma medicines on the market today, SPLUNC1 would not be a cure for asthma. Introducing the protein could effectively serve as a preventive measure that brings the airway back to its normal, healthy state, and provide another tool to help millions of people breathe better.

—Daniel Lane

Daniel Lane covers science, medicine, engineering and the environment in North Carolina.

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