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Dr. Ruben Carbonell examines the blood transfusion filter he helped develop. It will be manufactured under the trade name P-Capt® Filter by MacoPharma. Photo by Roger Winstead. |
For the first time, experimental results indicate that it is possible to use a resin filter to remove harmful prion proteins from the blood of an infected animal, a finding that has major implications for the removal of infectious prion proteins – the agents associated with variant Creutzfeldt-Jakob disease, mad cow disease, scrapie and other prion diseases in animals – during blood transfusions.
Dr. Ruben Carbonell, Frank Hawkins Kenan Professor of Chemical and Biomolecular Engineering and director of the Kenan Institute for Engineering, Technology and Science at North Carolina State University, and scientists from the University of Maryland at Baltimore’s VA Medical Center, the American Red Cross and ProMetic BioSciences, a biotechnology company, developed small resin beads with molecules that are able to bind to harmful prion proteins. The beads serve as an adsorption filter, capturing the bad proteins and allowing other blood components to be effectively cleansed of the prion-disease-causing agents.
A paper describing the research was published in the Dec. 23/30 version of The Lancet.
In prion diseases, which are called transmissible spongiform encephalopathies, prion proteins unfold and cause plaques in animal and human brains. Transmission of prion diseases has impacted the availability and cost of blood donations, especially in Europe.
In the Lancet study, the researchers took the blood of scrapie-infected hamsters and removed the white blood cells using a device called a leukofilter. The leukoreduced blood was then passed through another filter containing the new resin particles engineered to capture the prion proteins. A group of disease-free hamsters was inoculated with the blood that passed through the leukofilter only. A second group was inoculated with the blood that passed through both the leukofilter and the prion-capture filter.
The researchers found that while leukoreduction itself removed a good deal of the bad proteins – approximately 72 percent – none of the nearly 100 hamsters inoculated with the leukoreduced, resin-filtered blood were infected with scrapie by the end of the 550-day test. Fifteen of 99 hamsters receiving leukoreduced blood not passed through the resin filter were infected with scrapie.
After the experiment was completed, the researchers analyzed the brains of hamsters still alive at the end of the testing period. No evidence of scrapie was discovered in brains of hamsters that were inoculated with the resin-filtered blood.
Aided by scientists in NC State’s Nonwovens Cooperative Research Center, located in the College of Textiles, Carbonell and his colleagues have now developed a new filter to remove prions from donated blood during transfusions. The device takes donated blood from a blood bag, passes it through several “sandwiches” of the prion-capture resin beads placed between nonwoven fabric membranes, and places the filtered blood in a separate blood bag prior to infusion into a patient or blood donation recipient.
The filter device, to be manufactured under the trade name P-Capt® Filter by MacoPharma, has received CE Mark regulatory approval in Europe.
Carbonell and his colleagues are now looking for ways of targeting other pathogens in blood such as Hepatitis A virus, B19 parvovirus and Hepatitis C virus. He says it should be possible to engineer new molecules that capture prion proteins and viruses and to place them on a single filter to further enhance the safety of blood transfusions.
The research was funded by Pathogen Removal and Diagnostic Technologies Inc. (PRDT), a joint venture of the American Red Cross and ProMetic BioSciences, owned in part by Carbonell and Dr. Robert Rohwer from the University of Maryland.
- kulikowski -
Note to editors: An abstract of the paper follows.
“Reduction in Infectivity of Endogenous Transmissible Spongiform Encephalopathies Present in Blood By Adsorption to Selective Affinity Resins”
Authors: Luisa Gregori, Brian C. Lambert, Robert G. Rohwer, VA Medical Center, University of Maryland at Baltimore; Patrick Gurgel, Peter Edwardson, Steven J. Burton, ProMetic BioSciences; Julia T. Lathrop, David J. Hammond, American Red Cross; Ruben Carbonell, North Carolina State University
Published: Dec. 23/30, 2006, in The Lancet
Abstract:
Background – Transmissible spongiform encephalopathies (TSE) can be contracted through blood transfusion. Selective adsorption of the causative agent from donated blood might be one of the best ways of managing this risk. In our study, affinity resin L13, which reduces brain-derived infectivity spiked into human red blood cell concentrate by around 4 log10ID50, and its equivalent, L13A, produced on a manufacturing scale, were assessed for their ability to remove TSE infectivity endogenously present in blood.
Methods – 500 mL of scrapie-infected hamster whole blood was leucoreduced at full scale before passage through the affinity resins. Infectivity of whole blood, leucoreduced whole blood (challenge), and the recovered blood from each flow-through was measured by limiting dilution titration.
Findings – Leucoreduction removed 72 percent of input infectivity. 15 of 99 animals were infected by the challenge, whereas none of the 96 or 100 animals inoculated with the final flow-throughs from either resin developed the disease after 540 days. The limit of detection of the bioassay was 0∙2 infectious doses per mL. The overall reduction of the challenge infectivity was more than 1∙22 log10ID. The results showed removal of endogenous TSE infectivity from leucoreduced whole blood by affinity ligands. The same resins adsorb normal and abnormal prion protein from human infections with variant, sporadic, and familial Creutzfeldt-Jakob disease, in the presence of blood components.
Interpretation – TSE affinity ligands, when incorporated into appropriate devices, can be used to mitigate the risks from TSE-infected blood, blood products, and other materials exposed to TSE infectivity.
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