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 What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Researchers devise microreactor to study formation of methane hydrate

23.08.2017 | Materials Sciences

ShAPEing the future of magnesium car parts

23.08.2017 | Automotive Engineering

New insights into the world of trypanosomes

23.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>