Featured Research

from universities, journals, and other organizations

Bio-engineered protein shows promise as new hemophilia therapy

Date:
October 27, 2011
Source:
Children's Hospital of Philadelphia
Summary:
A genetically engineered clotting factor that controlled hemophilia in an animal study offers a novel potential treatment for human hemophilia and a broad range of other bleeding problems. A research team took the naturally occurring coagulation factor Xa and engineered it into a variant that safely controlled bleeding in mouse models of hemophilia.

A genetically engineered clotting factor that controlled hemophilia in an animal study offers a novel potential treatment for human hemophilia and a broad range of other bleeding problems.

Bio-engineered protein safely controls bleeding in mice with hemophilia

The researchers took the naturally occurring coagulation factor Xa (FXa), a protein active in blood clotting, and engineered it into a novel variant that safely controlled bleeding in mouse models of hemophilia. "Our designed variant alters the shape of FXa to make it safer and efficacious compared to the wild-type factor, but much longer-lasting in blood circulation," said study leader Rodney A. Camire, PhD, a hematology researcher at The Children's Hospital of Philadelphia.

"The shape of the variant FXa changes when it interacts with another clotting factor made available following an injury," added Camire. "This increases the functioning of the protein which helps stop bleeding." Camire is an associate professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania.

The study appears online in Nature Biotechnology, and will be published in the journal's November 2011 print issue.

Hemophilia causes, effects and treatment

In hemophilia, an inherited single-gene mutation impairs a patient's ability to produce a blood-clotting protein, leading to spontaneous, sometimes life-threatening bleeding episodes. The two major forms of the disease, which occurs almost solely in males, are hemophilia A and hemophilia B, characterized by which specific clotting factor is deficient. Patients are treated with frequent infusions of clotting proteins, which are expensive and sometimes stimulate the body to produce antibodies that negate the benefits of treatment.

Roughly 20 to 30 percent of patients with hemophilia A and 5 percent of hemophilia B patients develop these inhibiting antibodies. For those patients, the conventional treatment, called "bypass therapy," is to use drugs such as factor VIIA and activated prothrombin complex concentrates (aPCCs) to restore blood clotting capability. But these agents are costly (as much as $30,000 per treatment) and not always effective. Camire added that, in the current animal study, they were able to show the variant protein is more effective at a lower dose than FVIIa.

Goal -- creating new treatment options for patients with hemophilia

The range of options for hemophilia patients could improve if the study results in animals were to be duplicated in humans. "The variant we have developed puts FXa back on the table as a possible therapeutic agent," said Camire. Naturally occurring (wild-type) FXa, due to its particular shape, is not useful as a therapy because normal biological processes shut down its functioning very quickly.

By custom-designing a different shape for the FXa protein, Camire's study team gives it a longer period of activity, while limiting its ability to engage in unwanted biochemical reactions, such as triggering excessive clotting. "This potentially could lead to a new class of bypass therapy for hemophilia, but acting further downstream in the clot-forming pathway than existing treatments," said Camire, who has investigated the biochemistry of blood-clotting proteins for more than a decade.

When infused into mice with hemophilia, the FXa variant reduced blood loss after injury, as it safely restored blood clotting ability. Further studies are necessary in large animal models to determine whether this approach can become a clinical treatment for hemophilia patients who have developed inhibitors, or even more broadly as a drug for uncontrolled bleeding in other clinical situations.

Study funding and co-authors

Funding support for this research came from the National Institutes of Health, Pfizer Inc., and the National Hemophilia Foundation. The first author of the study was Lacramioara Ivanciu, PhD, of The Children's Hospital of Philadelphia. Other co-authors with Camire were from Children's Hospital, Pfizer Inc., and the Perelman School of Medicine of the University of Pennsylvania.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lacramioara Ivanciu, Raffaella Toso, Paris Margaritis, Giulia Pavani, Haein Kim, Alexander Schlachterman, Jian-Hua Liu, Valerie Clerin, Debra D Pittman, Rosalind Rose-Miranda, Kathleen M Shields, David V Erbe, James F Tobin, Valder R Arruda, Rodney M Camire. A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia. Nature Biotechnology, 2011; DOI: 10.1038/nbt.1995

Cite This Page:

Children's Hospital of Philadelphia. "Bio-engineered protein shows promise as new hemophilia therapy." ScienceDaily. ScienceDaily, 27 October 2011. <www.sciencedaily.com/releases/2011/10/111023135717.htm>.
Children's Hospital of Philadelphia. (2011, October 27). Bio-engineered protein shows promise as new hemophilia therapy. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2011/10/111023135717.htm
Children's Hospital of Philadelphia. "Bio-engineered protein shows promise as new hemophilia therapy." ScienceDaily. www.sciencedaily.com/releases/2011/10/111023135717.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins