Could Two New Drug Targets Prevent Asthma Attacks?

Two new drug targets could help to improve the wellbeing of millions of asthma sufferers. This is according to scientists from Brigham and Women’s Hospital, who say these drug targets in the inflammatory response pathway are responsible for asthma attacks, and can help wellness experts to develop the next big advance in treatment.

For the study, which was published in Science Translational Medicine, the researchers examined the lungs and blood of 22 people with mild and severe asthma. They discovered that two types of immune cells played significant roles in airway inflammation in the participants with severe asthma. The first was natural killer cells, which work by encouraging eosinophils, the programmed cell death in immune cells, and thus decrease airway inflammation. Type 2 innate lymphoid cells, on the other hand, secrete cell-signalling molecules called interleukin-13 which promotes airway inflammation.

A molecule called lipoxin A4, which is responsible for resolving inflammation, was found to control both mechanisms by acting in both pro-resolving and anti-inflammatory ways. The study investigators noted that lipoxin A4 encourages natural killer cells to decrease inflammation, but, by blocking interleukin-13 secretion, lipoxin A4 also discourages type 2 innate lymphoid cells from promoting inflammation.

According to senior study author Bruce Levy, MD, Pulmonary and Critical Care Medicine Division, BWH Department of Internal Medicine, ‘Stopping airway inflammation is similar to putting out a forest fire. Fire-fighters tackle forest fires in two ways — dousing the fire with water and clearing away dry brush that could fuel the fire. Lipoxin A4 does just that to resolve inflammation. It is an airway inflammation fighter that performs the double duty of dampening pathways that ignite inflammation while at the same time clearing away cells that fuel inflammation.’

Levy added, ‘Most patients with severe asthma have chronic airway inflammation that never fully resolves. This can lead to daily and often disabling symptoms despite available therapies. Our study provides new information on cellular targets that regulate inflammation and will enable the development of lipoxin-based therapeutics to decrease chronic inflammation in asthma and other diseases.’

Levy’s team has already discovered that lipoxin A4 production was defective in patients with severe asthma, but with their new findings they may have provided scientists and drug manufacturers with a way to boost lipoxin A4 in severe asthmatics, and thus design the next-generation of asthma therapies.