Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers harness the power of plants to fight hemophilia

31.03.2010
Hemophilia, a disease linked with legends of European monarchs, frail heirs and one flamboyant charlatan called Rasputin, still afflicts many people today.

And the very treatments that can help can also put patients' lives at risk.

The standard treatment is infusion with an expensively produced protein that helps the blood to clot. But in some patients the immune system fights the therapy, and in a subset of those, it sets off an allergic reaction that can result in death.

Now researchers at the University of Florida and the University of Central Florida have devised a way that potentially could help patients develop tolerance to the therapeutic protein before they are in need of treatment.

They genetically modified plants to encapsulate the tolerance-inducing protein within cell walls so that when ingested, it can travel unscathed through the stomach and be released into the small intestines where the immune system can act on it. The low-cost plant-based system, now being tested in mice, eventually could help improve the lives of many people who have hemophilia and dramatically reduce related health-care costs. The approach also has the potential for use with other conditions such as food allergies and autoimmune diseases.

"We're hoping that our research will, in the future, result in better and more cost-effective therapies," said Roland Herzog, Ph.D., an associate professor of pediatrics, molecular genetics and microbiology in the UF College of Medicine and a member of the UF Genetics Institute, who was one of the study's leaders.

The findings were published Monday in the 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 hemophilia can suffer from spontaneous internal bleeding or severe bleeding resulting from minor injuries. Males get the disease, which is linked to the X chromosome, while females are "carriers" who rarely exhibit symptoms. The two forms of the disease — hemophilia A and B — are associated with the absence of proteins called factor VIII and factor IX, respectively.

Many people around the world have the disease — 1 in 5,000 boys are born with hemophilia A, the more common of the two forms.

Hemophilia treatment consists of infusing the missing protein into a patient's blood. But in 25 percent of patients, the immune system rejects the therapy and makes inhibitors that stop the clotting factor from taking effect.

In hemophilia B, up to 4 percent of patients develop inhibitors to the protein therapy and many develop severe systemic allergic reactions, called anaphylaxis, which can be life-threatening.

"If the very protein that you administer to the patient is neutralized, it's as if you haven't administered any protein at all," said Thierry Vandendriessche, Ph.D., an associate professor of medicine at the University of Leuven in Belgium, and president of the European Society of Gene Cell Therapy. He was not involved in the study.

Because treatment itself poses a potential threat to life, it has to be done in a hospital setting under supervision. That makes it an expensive enterprise that often includes blood transfusions and hospital stays costing up to $1 million. Average treatment costs are $60,000 to $150,000 a year, according to the National Hemophilia Foundation.

To help patients tolerate therapy, doctors try to exhaust patients' immune systems by administering the therapeutic protein intravenously at frequent intervals and for long periods until the body no longer responds by producing inhibitors. While that brute force approach works for hemophilia A, it often doesn't for hemophilia B, in which patients risk death from anaphylactic shock if exposed to the protein therapy.

To find a new, gentler approach to developing tolerance, Herzog teamed with Henry Daniell, Ph.D., a Pegasus professor and University Board of Trustees Chair in the College of Medicine at the University of Central Florida, who has spent the last two decades developing transgenic plants for producing and delivering oral vaccines and immune-tolerant therapies.

They inserted the gene responsible for producing the therapeutic protein into the genome of plants. To maximize the amount of protein produced, they inserted thousands of copies of the genes into chloroplasts — the energy-producing centers of plants — using a gene gun.

The research team, including first authors Dheeraj Verma, Ph.D., and Babak Moghimi, M.D., fed the encapsulated protein to hemophilic mice for an extended period. Surrounded by the hardy plant cell walls, the protein was protected from digestive acids and enzymes while traveling through the stomach. Once it arrived safely in the small intestines, however, surrounding bacteria chewed on the cell walls, causing the protein to be released and acted on by the immune system to induce tolerance.

When the mice were later treated intravenously with the clotting factor therapy, they produced little or no inhibitors, and none developed anaphylactic shock.

"We have made them develop tolerance, and removed the allergic part of this treatment," Daniell said.

Not only did the pretreated mice survive the once-deadly treatment — they also had a greater positive effect from therapy than did other mice.

"You may wonder, 'why hasn't this happened before,'" Vandendriessche said. "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."

The researchers will continue to study how their method works, extend the approach to treating hemophilia A in mice and, ultimately, conduct trials in humans. Protein used in the human trials will be produced in lettuce and formulated to allow delivery of standard doses.

Czerne M. Reid | EurekAlert!
Further information:
http://www.ufl.edu

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>