Navigation Links
Bioengineered protein shows preliminary promise as new therapy for hemophilia
Date:10/23/2011

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.

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, Ph.D., 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 today in Nature Biotechnology, and will be published in the journal's November 2011 print issue.

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.

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.


'/>"/>

Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

Related biology news :

1. Bioengineered materials promote the growth of functional vasculature, new study shows
2. Photonic crystal biosensors detect protein-DNA interactions
3. Penn biophysicists create new model for protein-cholesterol interactions in brain and muscle tissue
4. Dont forget the vitamin A when working with its carrier protein
5. Saliva proteins could help detection of oral cancer
6. The structure of the Mre11 protein bound to DNA
7. New lab manual focuses on essential methods for purifying and characterizing proteins
8. Proteins in sperm unlock understanding of male infertility says new study
9. Response to immune protein determines pathology of multiple sclerosis
10. Columbia to award 2008 Horwitz Prize to Arthur Horwich & Ulrich Hartl for cellular protein folding
11. Human protein atlas will help pinpoint disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/15/2016)... , June 15, 2016 ... market report titled "Gesture Recognition Market by Application Market - Global ... 2016 - 2024". According to the report, the  global ... billion in 2015 and is estimated to grow ... 48.56 billion by 2024.  Increasing application ...
(Date:6/2/2016)... The Department of Transport Management (DOTM) ... million US Dollar project, for the , Supply ... Enrolment, and IT Infrastructure , to ... implementation of Identity Management Solutions. Numerous renowned international vendors participated ... was selected for the most compliant and innovative ...
(Date:5/20/2016)... -- VoiceIt is excited to announce its new marketing ... working together, VoiceIt and VoicePass will offer an ... slightly different approaches to voice biometrics, collaboration between ... Both companies ... "This marketing and technology partnership allows VoiceIt ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016   EpiBiome , a precision microbiome engineering ... debt financing from Silicon Valley Bank (SVB). The financing ... advance its drug development efforts, as well as purchase ... "SVB has been an incredible strategic partner to us ... bank would provide," said Dr. Aeron Tynes Hammack ...
(Date:6/23/2016)... Ky. , June 23, 2016 ... two Phase 1 clinical trials of its complement ... placebo-controlled, single and multiple ascending dose studies designed ... pharmacodynamics (PD) of subcutaneous injection in healthy adult ... subcutaneously (SC) either as a single dose (ranging ...
(Date:6/23/2016)... San Francisco, CA (PRWEB) , ... June 23, ... ... capture (EDC) software, is exhibiting at the Pennsylvania Convention Center and will showcase ... DIA Annual conference. ClinCapture will also be presenting a scientific poster on Disrupting ...
(Date:6/23/2016)... June 23, 2016 ReportsnReports.com ... report to its pharmaceuticals section with historic and ... and much more. Complete report on ... pages, profiling 15 companies and supported with 261 ... http://www.reportsnreports.com/reports/601420-global-cell-culture-media-industry-2016-market-research-report.html . The Global Cell ...
Breaking Biology Technology: