The findings suggest that compounds that block the neuropeptide Y (NPY) molecule, already developed for other conditions, may be a novel therapeutic strategy for asthma patients, especially those who are unresponsive to current standard therapies.
The research paper, “Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness,” was published in the Journal of Clinical Investigation.
Asthma, one of the most common chronic diseases, currently affects about 25 million people in the U.S., according to the National Heart, Lung, and Blood Institute. The disorder can be divided into disease with and without an immune response. Current therapies, such as corticosteroids and long-acting beta-agonists (LABA), are often ineffective on non-immune disease. The molecular mechanisms that drive this type of asthma are still poorly understood.
Researchers conducted studies in mice and found that when certain genes involved in lung epithelial development are inactivated, it results in an asthma phenotype, characterized by airway hyper-responsiveness (AHR) without inflammation caused by specific immune cells that are involved in immune-induced asthma.
The team also observed that the loss of these genes led to the overexpression of NPY, a molecule found in the airways of asthma patients, but whose role in disease pathogenesis remains unclear.
“NPY’s biological actions include stimulating the constriction of blood vessels,” explained Dr. Reynold A. Panettieri, one of the study’s authors, in a news release. “Previous research has linked variants of its gene to increased asthma risk, but NPY hasn’t been known previously to have a direct role in asthma.”
The research team tested human lung airway samples with NPY, and found that it induced airway contractility and airway narrowing, a definite aspect of asthma. On the other hand, loss of NPY markedly decreased AHR. Such findings lead researchers to believe that NPY causes AHR, and that the molecule may have an important causative role in human asthma.
NPY inhibitors have been developed by pharmaceutical companies for other conditions, such as obesity and hypertension. The researchers now believe that inhibiting NPY activity in people with asthma, as well as treatment with inhaled medication, might help patients cope with the condition, especially those who experience little to no relief from current therapies.
“Testing whether these NPY inhibitors would help human asthma patients is an exciting next step in developing a new drug therapy for asthma patients,” Panettieri said.
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