Advancing a protein drug in lettuce leaves to treat pulmonary arterial hypertension

Advancing a protein drug in lettuce leaves to treat pulmonary arterial hypertension

Reviewed by Kate Anderton, B.Sc. (Editor) Feb 16 2020 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 around the rest of the body. The condition is rare but deadly, and current treatments are expensive and have side effects and inconvenient modes of delivery. There is no cure. With a goal of developing a more effective, convenient, and affordable therapy, research led by Henry Daniell of Penn's School of Dental Medicine produced a protein drug in lettuce leaves to treat PAH. He worked with other scientists, including Steven M. Kawut of Penn's Perelman School of Medicine; Tim Lahm from the Indiana University School of Medicine; Maria Arolfo and Hanna Ng of the Stanford Research Institute, on toxicology and pharmacokinetic studies; and Cindy McClintock and Diana Severynse-Stevens of 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 an animal model of PAH, 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 with PAH. The team's findings appear in the March issue of the journal Biomaterials . We completed extensive investigations to highly express these proteins in lettuce plants and to ensure the product is safe and effective. We're ready to progress with further work to move this to the clinic." Henry Daniell, Penn's School of Dental Medicine Daniell has employed his innovative platform to grow biomedically important proteins of many kinds in the leaves of plants. The system works by physically 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 from which the researchers can harvest, dry, and process the leaves, resulting in a powder that can be placed in a capsule or suspended in a liquid for use as an oral medication. A 2014 publication in the journal Hypertension , on which the current study was based, earned Daniell a prize from the American Heart Association, and support from the National Institutes of Health through its Science Moving TowArds Research Translation and Therapy (SMARTT) program, which aims to efficiently translate promising basic science 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 pulmonary arterial hypertension, could significantly reduce the animals' pulmonary artery pressure while also improving cardiac function. Related Stories



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