- Study identifies that the levels of a protein SPLUNC1, are markedly low in asthmatics.
- Restoring the levels of this protein helped to reverse the hyper-sensitiveness to allergens in asthma.
- The protein SPLUNC1 could be a potentially new target for treating asthma which most relies on inhalers for treatment.
A protein has been identified which when missing or depleted, can cause airway constriction, production of mucus, chest tightness, and difficulty breathing in asthma.
The findings are by the researchers from the University of North Carolina (UNC).
‘Replenishing the whole protein or part of the protein, SPLUNC1 by delivering it via a nebulizer or inhaler could be a potential therapy for asthma.’
This discovery may lead to more effective treatments for asthma.
Around the world, an estimated 334 million people suffer from asthma and this condition is responsible for 250,000 annual deaths.
In the U.S one in 12 people, around 25 million, or 8% of the population had asthma in 2009. The cost of asthma to the health care system in the U.S. is very high.
"Most of the asthma therapies people use are inhalers, which have been around for decades. There have only been a few new asthma medications in the past 10 or 20 years, and they're still being evaluated. This protein could be a potentially new target to go after, and it could really benefit a lot of people." said Robert Tarran.
Role of Protein
Robert Tarran, PhD, associate professor of medicine, and a member of the UNC Marsico Lung Institute and colleague Steve Tilley, MD, UNC associate professor of medicin identified a protein, SPLUNC1
while they were studying cystic fibrosis and wondered what role it might play in asthmatics.
"We first measured SPLUNC1 levels in airway samples obtained from asthmatics and normal volunteers in the UNC Center for Environmental Medicine, Asthma, and Lung Biology," Tilley said. "We were astonished to find that SPLUNC1 levels were markedly reduced in people who have asthma."
This protein is produced by the epithelial cells that line the airways.
To test the role of the protein, researchers used mouse models that were given allergens similar to people who suffer from asthma.
The levels of SPLUNC1 were found to be depleted in the airways, similar to the findings in humans with asthma, and restoring SPLUNC1 reversed airway hyper-responsiveness, which is a cardinal feature of asthma.
SPLUNC1 work at a mechanical level by regulating the contraction of the airway smooth muscle by preventing a calcium entry into smooth muscle cells.
"People have been studying SPLUNC1 and its role in the context of other diseases, such as cystic fibrosis and lung cancer, but we believe that we are the group to identify its role in asthma," Tarran said.
"We found that this protein, which is actually turned off by excessive inflammation, is needed to cause the muscle to relax. It's essentially a muscle-relaxing factor that's missing from asthma patients. It's something that normally acts as a brake," Tarran said.
Crystal Structure of the Protein
Matt Redinbo, PhD, a professor of biochemistry and biophysics, and microbiology and immunology at the UNC School of Medicine, identified the crystal structure of SPLUNC1, which is the key in developing the next steps of this research.
"Since we know the crystal structure of the protein, we're able to find the active site of the protein that regulates smooth muscle contraction," Tarran said.
The next step would be to develop certain peptides or drugs that target the active site of the protein.
"If we can further establish that SPLUNC1 is the elusive epithelial-derived relaxing factor that is deficient in asthmatics, then we can begin working on ways to restore SPLUNC1 levels in patients as a novel therapy to treat asthma," Tilley said.
The findings are published in Nature Communications
- ASTHMA STATISTICS - (http://www.aaaai.org/about-aaaai/newsroom/asthma-statistics)
- Robert Tarran et al. Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor. Nature Communications ; (2017)