Rabinovitch awarded $10.8 million grant

Marlene Rabinovitch

Marlene Rabinovitch

A School of Medicine research team led by Marlene Rabinovitch, MD, has been awarded a five-year, $10.8 million grant from the National Heart, Lung and Blood Institute for the study of a novel drug therapy’s ability to treat three distinct lung problems.

“Our project was sparked by exciting preclinical data indicating that the elastase inhibitor elafin can be used to treat three of the most challenging lung conditions: pulmonary hypertension, ventilator-induced injury of the immature lung and lung transplant rejection,” said Rabinovitch, who is a professor of pediatric cardiology and a pediatric cardiologist at Lucile Packard Children’s Hospital.

The drug at the center of the project, elafin, is a protein made by the human body that inhibits neutrophil elastase, a tissue-destroying enzyme secreted by immune cells during the inflammatory response. Although elastase can play a positive role in destroying invading bacteria, it can also destroy healthy tissue. The Stanford team will test whether, by blocking elastase, elafin prevents such lung damage or promotes healing of damaged tissue in three lung diseases.

The grant will fund one project for each disease, all three of which are notoriously difficult to treat.

Rabinovitch will lead Project 1 on pulmonary hypertension, or elevated blood pressure in the arteries that supply blood to the lungs, which kills more than 60 percent of patients within five years of diagnosis.

Project 2 will focus on ventilator-induced injury of the immature lung, which causes lasting lung damage in premature babies. This project will be led by Richard Bland, MD, professor of neonatology.

Project 3, which is to be led by Mark Nicolls, MD, associate professor of pulmonary and critical care medicine and chief of the Division of Pulmonary and Critical Care Medicine, examines chronic lung transplant rejection, which leads lung transplant recipients to have the worst survival statistics of all organ recipients.

The researchers said that they plan to test elafin in animal models of each disease in conjunction with other therapies tailored to each of the conditions. They hope their findings will enable future clinical trials of elafin in people with these diseases.

Rabinovitch’s multidisciplinary team includes Stanford and Packard Children’s scientists from neonatology, bioengineering, pediatric and adult pulmonary medicine, and biostatistics.

In addition to the three disease-focused research projects, the grant also funds two cores that will provide a foundation for specific project functions.

Rabinovitch will lead the administrative core, which will work to facilitate publication of study findings, postdoctoral training in lung translational medicine and the transition of elafin into clinical trials after the planned experimental animal research is complete.

The biomarker core is to be led by Carlos Milla, MD, associate professor of pediatric pulmonary medicine. Milla’s group will develop bioassays that will assess treatment efficacy for the three diseases in humans and help stratify patients for future clinical trials. The biomarker core also will organize the patient database and the project’s physiological studies of lung and vascular function.

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