Gene Therapy Could Potentially Stop Pulmonary Hypertension

In a recent study, researchers successfully used gene therapy in animal models to stop the progression of pulmonary hypertension, which currently has no cure.

Pulmonary arterial hypertension (PAH) is high blood pressure in vessels leading from the heart to the lungs caused by abnormal remodeling of the lung blood vessels. It is triggered by abnormal calcium levels within the vascular cells, according to a study published in Journal of the American College of Cardiology.

The sarcoplasmic reticulum calcium ATPase pump (SERCA2a) regulates calcium levels in vascular cells and keeps them from proliferating in the vessel wall.

"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 study author Jane A. Leopold, MD. "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."

Researchers evaluated the use of a new aerosol inhalation technique to deliver the SERCA2a gene, which was previously proven effective in a rodent model. However, this time researchers tested the technique in swine models.

Included in this study were 20 pigs randomized into a group that received the aerosolized viral vector with the SERCA2a gene or a group that received a saline spray. After 2 months, researchers conducted tests in order to see if the therapeutic genes were functioning in the vessels of the animals’ lungs.

According to the study, researchers found that the heart and lung function improved and abnormal cellular changes that caused pulmonary hypertension were reduced.

More research is needed to focus on the long-term efficacy and safety are needed prior to human clinical trials.

"I'm excited that there is a potential new treatment for patients with this deadly disease," concluded lead study author Roger J. Hajjar, MD. "By tailoring the gene therapy, it looks like we can halt the proliferation of smooth muscle cells in the blood vessels. This should help restore function and improve survival in human patients."