Producing pulmonary drugs in plant cells may allow for cheaper treatments

By David Douglas

NEW YORK (Reuters Health) - Encapsulating protein drugs in plant cells might be a new, more affordable way to deliver them, researchers say.

In murine studies, angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) bioencapsulated in plant cells were effective against pulmonary hypertension.

"Protein drugs are currently not available or affordable to the majority of the global population because of current methods of production, requirement for cold storage and injectable delivery," Dr. Henry Daniell told Reuters Health by email.

"In this research," he continued, "we show that protein drugs can be made in plant cells, stored at ambient temperature and delivered orally. In particular, we show that oral delivery of angiotensin converting enzyme 2 produced in plant cells arrested progression of pulmonary hypertension or prevented the onset of this disease."

In a proof of concept study reported online September 15 in Hypertension, Dr. Daniell of the University of Pennsylvania, Philadelphia and colleagues "took advantage of transplastomic technology that enables chloroplasts to generate high levels of therapeutic proteins within plant leaves," as they put it in the paper.

The researchers induced pulmonary hypertension in rats by monocrotaline administration. One group of animals was simultaneously treated with bioencapsulated ACE2 or Ang-(1-7). Oral feeding of the agents in these animals prevented the development of monocrotaline-induced pulmonary hypertension and improved associated cardiopulmonary pathophysiology.

In a separate set of experiments, drug treatment initiated after two weeks of pulmonary hypertension induction significantly arrested disease progression. It also prompted an improvement in right heart function, and a decrease in pulmonary vessel wall thickness.

These beneficial effects, the team points out, are in line with those previously shown with genetic interventions with ACE2/Ang-(1-7).

The researchers note that other drugs made in plant cells have already been approved by the U.S. Food and Drug Administration. Among these is taliglucerase alfa (Elelyso, Pfizer) made from an enzyme grown in carrot cells and used in the treatment of Gaucher disease.

Dr. Daniell, although unable to give specifics because of a confidentially agreement, added that a large pharmaceutical company is now involved in his research. "So, this new platform for low cost production and delivery of protein drugs is anticipated to reach the clinic, pretty soon."

In an accompanying editorial, Drs. Justin L. Grobe and Curt D. Sigmund of the University of Iowa in Iowa City note that many questions remain to be answered, but the study "is remarkable for demonstrating that inexpensive, transgenic plant-based production of beneficial protein products-at levels which can significantly affect cardiopulmonary disease progression in vivo-is possible."

SOURCES: http://bit.ly/1ozQVrF and http://bit.ly/1udDKSV

Hypertension 2014.

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