PHILADELPHIA — The Perelman School Medicine at the University of Pennsylvania has received a $12 million grant over five years from the National Institutes of Health to head up a multi-institutional study looking at the biology of asthma and other airway diseases. The goal of the research is to find new, druggable targets in the smooth muscles of the airway that could lead to more effective bronchodilators that prevent or reverse lung constriction for longer periods of time.
Current, long-term therapies for asthma keep the airways open for 12 hours to prevent attacks but at the same time desensitize a key cell surface receptor known as the G-coupled protein receptor (GCPR), limiting their efficacy. Here, researchers will devise new therapeutics that sustain such receptors, and increase efficacy to 96 hours or more.
“Our approach has been to investigate novel targets and molecules with the hopes of finding bronchodilators that won’t lose activity and remain effective in severe asthma and other airway diseases, like COPD. We want longer-lasting treatment options,” said Reynold A. Panettieri, Jr, MD, director of the Asthma Section in the division of Pulmonary, Critical Care and Allergy, and Principal Investigator for the NIH grant. “This grant will propel our research even further, as the team, under the Airways Biology Initiative here at Penn, work towards much-needed and new approaches to managing asthma, a particular area of interest that affects 26 million Americans a year.”
Bronchodilators are medications that relax the bronchial muscles for obstructive lung diseases, like asthma. Today, the disease costs the US about $56 billion in medical costs, lost work days, and even early deaths—some of which are caused by current medications. COPD, or chronic obstructive pulmonary disease, costs the US almost $30 billion, not including lost productivity.
Past studies by researchers from the Initiative have uncovered new mechanisms in the airway smooth muscles that can be exploited. Recent studies in Science Translational Medicine and British Journal of Pharmacology , for instance, defined that regulators of G protein coupled signaling control smooth muscle contractile responses and promote smooth muscle cell growth—two findings that could serve as the basis for therapeutic targets in obstructive lung diseases.
The new research endeavor will elaborate on these discoveries and investigate other unique molecules that promote bronchodilation, new agonists to bitter taste receptors, and antagonists to GCPR to prevent bronchoconstriction.
Other institutions involved in the research include Thomas Jefferson University, the University of Southern Florida, Johns Hopkins University, and the University of Arkansas. The Program Project Grant (PPG) was awarded by the NIH’s National Heart, Lung and Blood Institute (1P01HL114471).
The PPG is more complex in scope and budget than the individual research grant. While individual research grants are awarded to support the work of one principal investigator who, with supporting staff, is addressing a scientific problem, program project grants are available to a group of several investigators with differing areas of expertise who wish to collaborate in research by pooling their talents and resources. PPGs represent synergistic research programs that are designed to achieve results not attainable by investigators working independently.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.