Drug also shows promise for helping to alleviate lung and cardiac symptoms associated with COVID-19
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 have side effects and are expensive and inconvenient to administer. 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 produced a protein drug in lettuce leaves to treat PAH. He worked with colleagues from Penn's Perelman School of Medicine, Indiana University School of Medicine; Stanford Research Institute, and RTI International.
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. The findings appear in Biomaterials.
Coincidentally, ACE2 is the binding site for SARS-COV-2 entry into the lungs. 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 innovative platform to grow biomedically important proteins of many kinds in the leaves of plants. 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 2014 publication in Hypertension, on which the current study was based, earned Daniell an American Heart Association prize, and support from the NIH's Science Moving TowArds Research Translation and Therapy (SMARTT) program.
That earlier study showed that ACE2 and angiotensin (1-7) could be expressed in tobacco leaves; this study moved to a lettuce-based platform. The new work takes advantage of other advancements the Daniell lab has made during the last several years. He and colleagues have successfully devised methods to enhance expression of human genes in the plants and to remove the antibiotic resistance gene that is used to select for angiotensin-producing plants. They've also worked with a partner to produce genetically engineered plants in a production facility that adheres to FDA standards and completed third party toxicology/pharmacokinetic studies.
