Corporate Banner
Satellite Banner
Biologics & Bioprocessing
Scientific Community
Become a Member | Sign in
Home>News>This Article

Retrogenix Points to New Drug Target for Malaria in Children

Published: Thursday, June 06, 2013
Last Updated: Thursday, June 06, 2013
Bookmark and Share
The discovery reported this week in Nature.

Retrogenix has announced that its unique human cell microarray technology played a pivotal role in determining the molecular interaction that triggers severe malaria in children.

The discovery, reported this week in Nature, could lead to new therapies to combat a form of the disease that kills around one million children per year.

Though researchers have known for over a century that red blood cells infected with malaria parasites can kill their host by sticking to the sides of blood vessels, the binding mechanism associated with the most lethal forms of malaria was unknown.

Now, Retrogenix’s technology has enabled researchers from the University of Copenhagen, together with Seattle Biomedical Research Institute, the National Institute for Medical Research, Tanzania, and the University of Oxford, to show that the parasite binds a protein in blood vessel walls called endothelial protein C receptor (EPCR), which is involved with regulating blood coagulation and the inflammatory response.

Malaria parasites grow in red blood cells and stick to the endothelial lining of blood vessels through a large family of parasite proteins called PfEMP1.

This way, the parasite avoids being carried with the blood to the spleen, where it would otherwise be destroyed. One of the most aggressive forms of malaria parasite binds in brain blood vessels, causing a disease called cerebral malaria.

In 2012, three groups of researchers, including the teams at the University of Copenhagen and Seattle Biomedical Research Institute, showed that a specific type of PfEMP1 protein was responsible for cerebral binding and other severe forms of malaria infection. However, until now, the receptor to which it binds remained unknown.

“The first big challenge was to generate a full-length PfEMP1 protein in the laboratory,” says Assistant Professor Louise Turner at the University of Copenhagen. “Next, we utilized the technology developed by Retrogenix to examine which of over 2,500 human proteins this PfEMP1 protein could bind to.”

Of the 2,500 proteins screened, a receptor called endothelial protein C (EPCR) was the single solid hit. “A lot of work then went into confirming this binding in the lab and not least to show that parasites from non-immune children with severe malaria symptoms in Tanzania often bound EPCR,” she continues.

“It was a true eureka moment,” says Assistant Professor Thomas Lavstsen. “Under normal conditions, ECPR plays a crucial role in regulating blood clotting, inflammation, cell death and the permeability of blood vessels. The discovery that parasites bind and interfere with this receptor´s normal function may help us explain why severe symptoms of malaria develop."

Malaria parasites disrupt the important functions of blood vessels
Severe malaria symptoms such as cerebral malaria often result in minor blood clots in the brain. One of our body´s responses to malaria infection is to produce inflammatory cytokines, but too much inflammation is dangerous, describes Professor Joseph Smith, from the Seattle Biomedical Research Institute.

“ECPR and a factor in the blood called protein C act as a ‘brake’ on blood coagulation and endothelial cell inflammation and also enhance the viability and integrity of blood vessels, but when the malaria parasites use PfEMP1 to bind EPCR, they may interfere with the normal function of EPCR, and thus the binding can be the catalyst for the violent reaction,” he explains.

“Investigating this question is the next step to learn about how malaria parasites cause disease.”

Towards an intervention
The discovery that malaria parasites bind EPCR may advance vaccine and drug interventions to treat severe malaria.

Dr. Matthew Higgins from the University of Oxford explains: “Now that we know the pair of proteins involved, we can begin zooming further in to reveal the molecular details of how malaria parasites grab onto the sides of blood vessels. We want to know exactly which bits of the parasite protein are needed to bind to the receptor in the blood vessel wall. Then, we can aim to design vaccines or drugs to prevent this binding.”

Vaccine research will also benefit immediately from the discovery, since scientists can already now test the effectiveness of different vaccine candidates at preventing PfEMP1 from binding ECPR.

“Over the last decade, we have come to appreciate that specific PfEMP1 proteins are associated with different severe forms of malaria,” explains Professor Thor Theander at the University of Copenhagen. “Together with the National Institute for Medical Research, Tanzania, we are in the process of preparing phase I trials for a vaccine to prevent parasite binding in the placenta and malaria during pregnancy,” he explains.

This new discovery holds the potential for also developing a vaccine to reduce the heavy burden malaria disease inflicts on children. “It will be a long haul, but with these results, we can get started right away,” he says.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Retrogenix Co-founders Attend Reception at Buckingham Palace
HM the Queen welcomes winners of the 2015 Queen's Award for Enterprise.
Friday, July 31, 2015
Scientific News
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Surprising Trait Found in Anti-HIV Antibodies
Scientists at The Scripps Research Institute (TSRI) have new weapons in the fight against HIV.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
The Do’s and Don’ts of SPR Experiments
Surface Plasmon Resonance (SPR) is a technique that is becoming more widely used, particularly by anyone who wants to obtain accurate on (association) and off (dissociation) rates for biomolecular binding.
Genetically Engineering Algae to Kill Cancer Cells
New interdisciplinary research has revealed the frontline role tiny algae could play in the battle against cancer, through the innovative use of nanotechnology.
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Single Vaccine for Chikungunya, Related Viruses May be Possible
What if a single vaccine could protect people from infection by many different viruses? That concept is a step closer to reality.
Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Circadian Clock Controls Insulin and Blood Sugar in Pancreas
Map of thousands of genes suggests new therapeutic targets for diabetes.

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos