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 in pulmonary arterial hypertension (PAH). The condition is rare but deadly. Current treatments have side effects and are expensive and inconvenient to administer. And, there is no cure.
With a goal of developing a more effective, convenient, and affordable therapy, research led by Penn Dental Medicine’s Henry Daniell, PhD, has produced a protein drug in lettuce leaves to treat PAH. He worked with colleagues from Penn’s Perelman School of Medicine, the Indiana University School of Medicine, the Stanford Research Institute, and RTI International.
The protein drug can be taken orally. It comprises the enzyme angiotensin converting enzyme-2 (ACE2) and its protein product angiotensin (1-7). In a PAH animal model, it reduced pulmonary artery pressure and remodeling. Also, rigorous toxicology and dose-response studies suggested the drug’s safety in animals.
Coincidentally, ACE2 is the binding site for SARS-COV-2 entry into the lungs. A decrease of ACE2 in COVID-19 patients leads to acute lung and cardiac failure. Clinical trials are getting started to orally deliver ACE2 directly to the lungs to relieve these symptoms in COVID-19 patients.
Daniell has employed his platform to grow biomedically important proteins of many kinds in the leaves of plants, Penn Dental said. The system bombards plant tissue with the genes of interest, prompting chloroplasts to take up genes and then express that protein. Propagating those plants creates a kind of pharmaceutical farm from which the powdered plants can be encapsulated.
A previous study that formed the basis of the current study earned Daniell an American Heart Association prize and support from the National Institutes of Health’s Science Moving TowArds Research Translation and Therapy (SMARTT) program.
The earlier study showed that ACE2 and angiotensin (1-7) could be expressed in tobacco leaves. The newer study moved to a lettuce-based platform. It also takes advantage of other advances that Daniell’s lab has made in the last several years.
Daniell and his colleagues have successfully devised methods to enhance the expression of human genes in the plants and to remove the antibiotic resistance gene used to select for angiotensin-producing plants.
The researchers also have worked with a partner to produce genetically engineered plants in a production facility that adheres to Food and Drug Administration standards and completed third-party toxicology and pharmacokinetic studies.
The study, “Investigational New Drug Enabling Angiotensin Oral-Delivery Studies to Attenuate Pulmonary Hypertension,” was published by Biomaterials.
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