Filter Protects Blood Transfusions

Mad Cow Disease jolted the United Kingdom in the 1980s, crippling the beef industry and panicking the public as scores of people—not just cattle—succumbed to the insidious infection known in humans as variant Creutzfeldt-Jakob Disease (CJD). Eating tainted beef was the most obvious means of transmission for the disease, but blood transfusions were also seen as a potentially deadly source of infectivity. Research by Dr. Ruben Carbonell, Frank Hawkins Kenan Distinguished Professor of Chemical and Biomolecular Engineering, could soon significantly reduce the threat of contracting CJD from donated blood.

The human effects of Mad Cow Disease are similar to those of Alzheimer’s disease.

CJD is caused by an accumulation of misshapen proteins, called prions, in the brain. Prions are abnormally folded, and their presence induces other proteins to adopt abnormal structures. Prions form plaques similar to those in Alzheimer’s disease, creating holes in the brain tissue. The infection is incurable and fatal.

Fearing prions could be in blood donated by infected people, Red Cross officials destroyed countless units stored in blood banks and banned donations from anyone in the U.K. who received a transfusion after 1980. They also turned to Carbonell, who had been studying small molecules that bind to specific proteins, to help find a way to filter prion infectivity and ensure that donated blood could safely be given to patients in need.

In designing the filters, Carbonell tapped libraries of small molecules, using assays to pinpoint some that bind to prions. He then sequenced these molecules to determine their structure, so they could be replicated easily on a large scale. Porous plastic particles were then impregnated with the molecules, and the particles were sandwiched between membranes of nonwoven fabric using a process developed by the Nonwovens Cooperative Research Center in the College of Textiles. Several of these sandwiches were layered atop each other to create a prototype filter. A University of Maryland researcher working with Carbonell tested the device by giving infected blood to hamsters. The animals that received unfiltered transfusions all developed CJD-like conditions, while the hamsters that received filtered blood showed no signs of infection. “The results were quite stunning,” Carbonell says.

After extensive studies, a British safety panel recently recommended a final version of the filter for removing prions from donated blood, a key step to final adoption of the product in the U.K. Other countries, from Japan to France to Canada, also have expressed interest in the filters. “With the removal of prions from blood, the risk of CJD transmission during blood transfusions is significantly reduced,” Carbonell says. “This device will bring great peace of mind to patients requiring this vital treatment.”

 

Dr. Ruben Carbonell tapped libraries of small molecules to pinpoint some that would bind to the infective proteins in variant CJD so they could be filtered from donated blood before a transfusion.

Portions of a prion protein, right, unfold and adopt an abnormal structure and then induce normal protein molecules, like the one at left, to become misshapen as well.

Over 8 million units of blood are needed each year for transfusions in the U.S. and U.K. alone.