Plant-Based Inhibitor Therapy Continues to Evolve

Submitted by the National Hemophilia Foundation

Scientists from the University of Florida in Gainesville (UF-G) and the University of Pennsylvania (U-Penn) continue to investigate an experimental, plant cell-based approach to preventing inhibitors and allergic reactions (anaphylaxis) to clotting factor therapies in people with hemophilia. An update on their progress was published online, December 16, 2014, in Scientific American, a division of Nature America, Inc.

Lead investigator Henry Daniell, PhD, director of translational research at the U-Penn School of Dental Medicine, and Roland W. Herzog, PhD, a molecular biologist at UF-G, have, for several years, been working on a technique that involves encapsulating an orally administered “tolerance-inducing protein” such as factor IX (FIX) within plant cell walls. When ingested, the bio-encapsulated protein safely travels through the stomach before reaching the small intestines. The plant cell wall shields the FIX from being prematurely broken down by stomach acid. Eventually, microorganisms eat away the cell wall, gradually releasing the protein.

Building on earlier studies (2010) that successfully used bioengineered tobacco plant cells to prevent inhibitors and anaphylaxis in mice with hemophilia B (FIX deficiency), Daniell and Herzog are now turning to freeze-dried lettuce leaf cells engineered to trigger a high concentration of FIX. Each lettuce leaf cell contains approximately 10,000 chloroplasts, each structured in such a way to hold very large volumes of the FIX protein. Chloroplasts are subunits of plant cells, most often known as crucial components of photosynthesis. Although these chloroplast-rich plant cells are not equipped to prevent bleeding--plants are unable to make human clotting factors biologically active--they have shown an ability to induce tolerance in the immune system to FIX. Researchers have been developing this novel therapeutic approach for several years to create potential vaccines against malaria and cholera, and genetically engineered insulin to help prevent diabetes.

Daniell and Herzog recently took the next step and tested this approach in two dogs with hemophilia B. They fed both dogs their normal food along with the engineered lettuce cells converted into a green powder form. There have been no reports of anaphylaxis or inhibitors in the mice from the earlier study or in the dogs that recently received the plant-based therapy. “So far, it’s going very well,” reported Daniell. If this novel oral therapy continues to prevent treatment complications in animal models, the next step will be to replicate that success in human clinical studies.

Source: Scientific American, December 16, 2014