Scientists have used a novel gene therapy to halt the progression of pulmonary hypertension, a form of high blood pressure in the lung blood vessels that is linked to heart failure, according to a study published online ahead of print in the Journal of the American College of Cardiology (JACC).
“There is considerable need for new treatments that improve functional capacity, symptoms, and survival,” said Roger J. Hajjar, MD, professor of Medicine and director of the Cardiovascular Research Center at the Icahn School of Medicine at Mount Sinai. “This treatment with gene therapy offers a novel method of treating a deadly disease that disproportionately affects young adults and women,” he said. Female patients make up about 72 percent of the total population of patients with PAH.
“The therapeutic potential of using gene therapy to treat pulmonary hypertension by delivery of aerosolized adeno-associated virus carrying SERCA2a to directly target vascular remodeling through the overexpression of the SERCA2a protein is very significant,” said co-senior study author Jane A. Leopold, MD, of Brigham and Women’s Hospital, Harvard Medical School. “In addition, as other novel targets are identified by deep phenotyping of patients with pulmonary hypertension in the National Institutes of Health/National, Heart, Lung, & Blood Institute-funded Pulmonary Vascular Disease Phenomics (PVDOMICS) study, they may be viable candidates for aerosolized gene transfer using adeno-associated viral vectors.”
There were two primary objectives for this study, which was conducted by Mount Sinai and research teams from Brigham & Women’s Hospital in Boston, MA, and Centro Nacional de Investigaciones Cardiovasculares Carlos III in Madrid, Spain. First, scientists wanted to learn if it is feasible to deliver a therapeutic gene called SERCA2a in aerosol form to damaged blood vessels of the lung using an engineered adeno-associated virus as a “vector.” Second, they wanted to see if there was a sustained beneficial impact, and if the transferred genes effectively slowed or stopped the vascular changes in the airways that are the hallmark of PAH and other forms of pulmonary hypertension.
In the study, 20 pigs were divided into two groups, half of which received the aerosolized viral vector carrying the SERCA2a gene and half a saline spray. Two months after the gene delivery, scientists performed tests to see if the new therapeutic genes were present and functioning in the vessels of the animals’ lungs, and whether the transfer was producing the desired effects. When they examined the animals, they found that that heart and lung function had improved and abnormal cellular changes causing PH were reduced.