Advancing an Oral Drug for Pulmonary Arterial Hypertension

PHILADELPHIA: In pulmonary arterial hypertension (PAH), high blood pressure in the lungs' arteries causes the heart to work extra hard to pump blood to the lungs and the rest of the body.

The condition is rare but deadly, and current treatments are expensive and have side effects and inconvenient delivery modes. There is no cure.

With a goal of developing a more effective, convenient, and affordable therapy, research led by Dr. Henry Daniell of Penn Dental Medicine produced a protein drug in lettuce leaves to treat PAH. He worked with other scientists from Penn's Perelman School of Medicine, Indiana University School of Medicine, and Stanford Research Institute on toxicology and pharmacokinetic studies; and from RTI International on regulatory studies.

The protein drug, composed of the enzyme angiotensin converting enzyme-2 (ACE2) and its protein product angiotensin (1-7), can be taken orally and, in a PAH animal model, reduced pulmonary artery pressure and remodeling. In addition, rigorous toxicology and dose-response studies suggested the drug's safety in animals. Further work will be necessary to develop this novel treatment approach for patients. The team's findings appear in Biomaterials.

We completed extensive investigations to highly express these proteins in lettuce plants and to ensure the product is safe and effective, says Daniell.

Daniell has employed his innovative platform to grow biomedically important proteins of many kinds in the leaves of plants. The system works by bombarding plant tissue with the genes of interest, prompting chloroplasts into taking up genes and then stably expressing that protein. Propagating those plants then creates a kind of pharmaceutical farm with the leaves harvested, dried, and processed, resulting in a powder that can be encapsulated or suspended in liquid.

A 2014 publication in Hypertension, on which the current study was based, earned Daniell a prize from the American Heart Association, and support from the NIH through its Science Moving TowArds Research Translation and Therapy program, which aims to efficiently translate promising discoveries into therapies that can make a difference in people's lives.

That earlier publication had shown that ACE2 and angiotensin (1-7) could be expressed in tobacco leaves and, when fed to rats with a condition that models PAH, could significantly reduce the animals' pulmonary artery pressure while also improving cardiac function.
(PRN)

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Advancing an Oral Drug for Pulmonary Arterial Hypertension