Dr. Daniell Featured in Proceedings of the National Academy of Sciences
ORLANDO, April 30, 2010 — UCF College of Medicine Professor Henry Daniell’s use of genetically modified plants to treat hemophilia has been featured in the April 13 edition of the highly regarded Proceedings of the National Academy of Sciences.
Hemophilia is characterized by defects in the gene that produces a protein required for blood to clot. People with the disease can suffer from spontaneous internal bleeding or severe bleeding from minor injuries. However, treating the disease can be dangerous and even fatal because many patients suffer fatal allergic reactions to the expensive protein that doctors use to make their blood clot.
Now Dr. Daniell and his former graduate student, Dr. Roland Herzog, currently an associate professor at the University of Florida, have worked with plants to encapsulate a tolerance-inducing protein (clotting factor IX) within cell walls so that the protein can be ingested and safely travel through the stomach before it’s released into the small intestines where the immune system can act on it.
This low-cost, plant-based approach, which is now being tested in mice, eventually could help save people’s lives and dramatically reduce related health care costs. Their research also has the potential for use with food allergies and autoimmune diseases.
About 1 in 5,000 boys worldwide are born with the most common form of hemophilia, while women are “carriers” who rarely exhibit symptoms.
Current treatment consists of infusing the missing protein into patients’ blood. But 20 percent of patients’ immune systems reject the therapy and create inhibitors that stop the clotting from taking effect. A smaller percentage of patients develop life threatening allergic reactions. To help people tolerate therapy, doctors try to exhaust patients’ immune systems by administering the protein intravenously at frequent intervals and for long periods of time until the body no longer responds by producing inhibitors. But that treatment is still risky and must be conducted in hospital settings under supervision, making it an expensive enterprise that often includes blood transfusions and hospital stays costing up to $1 million.
After inserting the gene responsible for producing the therapeutic protein into the plants, Drs. Daniell and Herzog found that hemophilic mice fed the encapsulated proteins and later treated intravenously with the clotting therapy produced few or no inhibitors and none suffered anaphylactic shock.
“We have made them develop tolerance and removed the allergic part of this treatment,” Dr. Daniell said.
“You may wonder, ‘why hasn’t this happened before,'” said Dr. Thierry Vandendriessche, associate professor of medicine at the University of Leuven in Belgium, and president of the European Society of Gene Cell Therapy. “It’s because it was difficult to administer a high amount of protein in the right place and at the right time. I think this is a milestone — nobody has previously achieved such levels of robust immune tolerance by any means using a noninvasive procedure.”
For the past two decades, Dr. Daniell has developed transgenic plants for producing and delivering oral vaccines and immune-tolerant therapies. He has used similar techniques to create potential vaccines against malaria, cholera, anthrax and plague and genetically engineer insulin into plants to help prevent diabetes.