Scientists from Rutgers University and the University of Pennsylvania have identified a biological pathway that could explain why current asthma therapies often prove ineffective.
The discovery has the potential to lead to new treatments for many of the 25 million people in the U.S., including seven million children, who suffer from the chronic condition.
Researchers Reynold A. Panettieri, inaugural director of the clinical and translational science institute at Rutgers, and Edward E. Morrissey, director of the Penn Center for Pulmonary Biology, determined that when certain genes in mice were inactivated, the mice developed an asthma-like condition, exhibiting airway hyper-responsiveness, or AHR, a classic sign of asthma.
"We found that the airways of these mice did indeed behave like asthmatic human airways," said the researchers in a collaborative study appearing today in the Journal of Clinical Investigation.
Studying the cause of the AHR in the airways of these mice, the researchers next examined the gene patterns of the affected airway's epithelial cells. They found that the molecule neuropeptide, referred to as NPY, was present in more concentrated levels than in control mice. NPY is a signaling molecule and neurotransmitter found abundantly in the nervous system and some other parts of the body.
"NPY's biological actions include stimulating the constriction of blood vessels," Panettieri said. "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 investigators tested whether normal human lung airways exhibit a marked increased in hyper-responsiveness when exposed to NPY.
"These data strongly suggest that NPY can cause airway hyper-responsiveness in human lungs and could be a causative mechanism in human asthma," Morrisey said.
Panettieri also noted that the presence of NPY activates pathways within smooth muscle that provoke contraction and narrowing of the airway passages, a process that defines asthma.
The researchers said the findings suggest that inhibiting NPY activity in people with asthma, perhaps with an inhaled medication, might help the millions of patients who receive little or no relief from current asthma therapies.
Panettieri explained that pharmaceutical companies have already developed compounds that block NPY signaling for other conditions, such as obesity and hypertension.
"Testing whether these NPY inhibitors would help human asthma patients is an exciting next step in developing a new drug therapy for asthma patients," he said.
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Journal
Journal of Clinical Investigation