Asthma is characterized by excessive sensitivity of the lungs to stimuli (including infections, allergens and irritants) leading to inflammation of the airway and difficulty breathing. Millions of people worldwide suffer from asthma, and its prevalence is growing, making asthma a global public health concern.

There is no cure for asthma, although pharmaceutical intervention can help to manage symptoms by suppressing inflammation or dilating the airway to ease breathing. “Current asthma treatments can help to control symptoms and dampen airway inflammation; however, therapies are not available to promote the resolution of asthma,” said Bruce Levy, of Brigham and Women's Hospital (Boston, MA) in a press release. Now, results of a recent study led by Levy and Clifford Woolf, of Children's Hospital Boston and Harvard Medical School (Boston, MA), point toward a new approach to treating asthma. The results suggest that disabling a specific set of sensory neurons in the lungs, called nociceptors, can reduce airway inflammation and lung hypersensitivity (Neuron doi:10.1016/j.neuron.2015.06.007; published online 25 June 2015).

Nociceptors in the lungs trigger protective reflexes such as coughing in response to stimuli; nociceptors are also more abundant and more sensitive in people with asthma. Levy and Woolf's research team found that airway inflammation activates lung nociceptors and that this activation elicits a cascade of immune signals that intensifies inflammation and aggravates symptoms of asthma. The findings led to the hypothesis that interfering with nociceptor activation might have therapeutic benefits in asthma. The scientists tested this idea in mouse models of acute and chronic asthma by silencing nociceptors either genetically or pharmacologically. Silencing of nociceptors substantially reduced airway inflammation and lung hypersensitivity in the mice.

The pharmacological compound tested in the study is called QX-314. It is related to lidocaine, which is used as a local anesthetic because it blocks nerve signaling. Lidocaine has been tested as an asthma treatment, but it can have adverse outcomes because it affects all neurons. QX-314 is modified such that it specifically targets nociceptors that are activated by inflammation, including those in the lung, and does not readily enter the bloodstream. These properties reduce the compound's potential to cause side effects and extend its duration of action, improving its prospects for treating asthma.

“We are sufficiently encouraged by the strong relief of lung inflammation and airway constriction to actively embark on a major drug development program, with the aim of clinically testing this strategy [QX-314] for multiple allergic conditions,” said Woolf in a press release.