Pulmonary Arterial Hypertension May Be Treatable with Inhaled Gene Therapy

Pulmonary Arterial Hypertension May Be Treatable with Inhaled Gene Therapy

Researchers managed to halt the progression of pulmonary arterial hypertension (PAH) using a specific gene therapy approach in a pig model of the disease. The findings mean that in the future, gene transfer via aerosol inhalation may be used as a potential therapy for PAH and other related lung diseases.

“There is considerable need for new treatments that improve functional capacity, symptoms, and survival,” said the study’s senior author, Dr. Roger Hajjar, M.D., of Mount Sinai Hospital, New York, in a news release. “This treatment with gene therapy offers a novel method of treating a deadly disease that disproportionately affects young adults and women.”

The research team, led by Hajjar, used the harmless adeno-associated virus (AAV) to deliver a gene called SERCA2a to the lungs via an inhaled aerosol form. Researchers used a pig model that closely resembles PAH in humans, and observed that in animals receiving the virus carrying the SERCA2a gene, heart and lung function improved, and the abnormal cellular changes causing PAH were reduced. This is the first time a successful gene delivery has been shown to change the course of PAH in a large animal model.

“I’m excited that there is a potential new treatment for patients with this deadly disease,” Hajjar said. “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.”

PAH is a rare, rapidly progressing disease affecting around 150,000 people in America every year. The disease mainly affects women, and 50 percent of those diagnosed die within five years due to heart failure.

The high blood pressure observed is caused by the thickening and narrowing of the blood vessels going from the heart to the lungs. The abnormal remodeling of the lung blood vessels is due to faulty calcium regulation in the cells. This results in chronically high levels of calcium in the lung blood vessels, leading to aberrant cell division, and therefore thickening of the vessels. SERCA2a is a key modulator of calcium cycling of the cardiovascular system, and is known to be down-regulated in PAH.

The findings were described in the study “Intratracheal Gene Delivery of SERCA2a Ameliorates Chronic Post-Capillary Pulmonary Hypertension: A Large Animal Model,” published in the Journal of the American College of Cardiology.

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