Potential Target Identified for Future Asthma Treatments

A new discovery may lead to improved treatment options for asthma.

In a study published inNature Communications, investigators identified the protein short palate and nasal epithelial clone 1 (SPLUNC1), which could play a critical role in regulating proper airway function.

The investigators first measured SPLUNC1 levels in airway samples obtained from asthmatics and healthy volunteers in the UNC Center for Environmental Medicine, Asthma, and Lung Biology, according to a UNC press release.

“We were astonished to find that SPLUNC1 levels were markedly reduced in people who have asthma,” said investigator Steve Tilley, MD.

Next the investigators used mouse models that were given allergens similar to the ones found in individuals withasthma.

The results of the study showed that levels of SPLUNC1 were depleted in the airways—–similar to humans with asthma––and restoring SPLUNC1 reversed airway hyper-responsiveness, a cardinal feature of asthma, according to the authors.

The investigators concluded that SPLUNC1 could regulate airway smooth muscle contraction by preventing calcium from entering into smooth muscle cells, explaining how a deficiency in the protein may lead to airway hyper-responsiveness.

“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,” said investigator Robert Tarran, PhD.

A potential treatment for asthma could be to replenish the whole protein or a part of it through a nebulizer or inhaler, according to the authors.

“Instances of asthma are much higher in the western world,” Tarran said. “Some of the highest countries are Australia, the UK, and the States. The cost of asthma to the health care system in the US is quite big. 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 being evaluated. This protein could be a potentially new target to go after, and could really benefit a lot of people.”

A crucial part of the study was investigator Matt Redinbo’s, PhD, identification of SPLUNC1 crystal structure, according to the press release.

“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. “So we can make peptides or drugs to target that active site and see if that works. That’s one approach.”

To study their hypothesis in patients, investigators have submitted an application for a National Institutes of Health grant.

“We want to study this in patients to correlate SPLUNC1 levels with airway hyper-reactivity,” Tarran said. “And we also want to go deeper into the mechanism—–how does this protein do what we observed. So there are several future avenues of research: expanding clinical studies, designing drugs in mouse studies, and then studying the underlying biology of what happens in a person with asthma.”

Tilley added, “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. I am looking forward to working with Drs. Neil Alexis, Ilona Jaspers, and David Peden in our asthma center to design more translational studies in humans so that we can determine the clinical significance and therapeutic potential of SPLUNC1 in asthma.”