CINCINNATI—A team of University of Cincinnati (UC) researchers will use a grant of almost $1.6 million from the National Heart, Lung, and Blood Institute of the National Institutes of Health to study the rare lung disease pulmonary alveolar microlithiasis (PAM).
The grant will be made over a four-year period and the principal investigator for the project is Frank McCormack, MD, Taylor Professor and Director of the Division of Pulmonary, Critical Care and Sleep Medicine at the UC College of Medicine.
"Genetic mutations result in loss of a key phosphate transporter in the lungs. Defective genes must be inherited from both parents, so the disease is more prevalent in regions where intermarriage within families occurs,” explains McCormack.
There have been about 700 recorded cases of pulmonary alveolar microlithiasis in the medical literature. McCormack said the "lung stones” are actually crystals composed of calcium phosphate that cause irritation and scarring in the airspaces of the lung. The disease reduces life expectancy by several decades and is often fatal.
"We have created a mouse model that closely mimics the human condition,” says McCormack. "We are trying to understand the cause of the disease and to use the mouse as a platform to design trials. We have some exciting practical ideas for treatment that we are anxious to bring to the bedside.”
The mouse model was developed by Atsushi Saito, MD, PhD, a postdoctoral fellow at UC, with assistance from Nikolaos Nikolaidis, PhD, senior research associate at UC. Other collaborating researchers include the following individuals: Jim Bridges, PhD, assistant professor in the Department of Pediatrics at UC and researcher at Cincinnati Children’s Hospital Medical Center; Jason Woods, PhD, professor in the Department of Pediatrics at UC and director, Center for Pulmonary Imaging Research at Cincinnati Children’s Hospital Medical Center; and Hassane Amlal, PhD, research associate professor in the Department of Internal Medicine at UC.
To confirm that findings in the mice are relevant to humans, McCormack said his team is collecting blood samples from sites participating in the Rare Lung Diseases Consortium in the United States, Croatia, Spain, Turkey and Japan.
"In rare disorders, we can study disease pathogenesis from the vantage point of a known molecular defect.” says McCormack. "Rapid progress is possible and discoveries made in the orphan disease can shed light on more common disorders. For example, the anti-GM-CSF auto-antibody found to cause the rare lung disease alveolar proteinosis is now being trialed in a number of autoimmune disorders.”
McCormack is also director of the pulmonary branch of the UC Heart, Lung and Vascular Institute. The UC Heart, Lung and Vascular Institute is a partnership between UC Health and the University of Cincinnati College of Medicine designed to connect expert physicians with cutting edge researchers to make breakthroughs in medicine.
The National Heart, Lung and Blood Institute of National Institutes of Health provided funding for McCormack’s research under the award number R01HL127455.