Managing the risks from blood-associated TSE infectivity with prion affinity ligands

I&EC 49

Robert Rohwer, rrohwer@umaryland.edu1, Luisa Gregori2, Brian C. Lambert1, Ruben G Carbonell, ruben@ncsu.edu3, Patrick V. Gurgel4, David Hammond5, Julia Lathrop6, Peter Edwardson7, and Steve J. Burton1. (1) Department of Neurology, University of Maryland at Baltimore, 10 N. Greene Street, Baltimore, MD, MD 21201, (2) Medical Research Service 151, Veterans Affairs Medical Center, Baltimore, MD 21201, (3) Department of Chemical and Biomolecular Engineering, North Carolina State University, P.O. Box 7905, Raleigh, NC 27695, (4) Department of Chemical and Biomolecular Engineering, ProMetic Life Sciences and NC State University, 8168 chemin Montview, 911 Partners Way, Mont-Royal, QC H4P 2L7, Canada, (5) American Red Cross, (6) Prolias, Laytonsville, (7) ProMetic Life Sciences, 8168 chemin Montview, 911 Partners Way, Mont-Royal, QC H4P 2L7, Canada
Since 1996 there have been over 200 cases of a distinctive variant (vCJD) of a rare human TSE called Creutzfeld-Jakob disease (CJD) that are almost certainly BSE infections of humans. To date there have been four recognized cases of secondary transmission of vCJD in humans by transfusion. Based on our earlier quantitative studies of the titer and distribution of TSE infectivity in rodent blood we began development of a removal strategy for all forms of the human prion protein, infected and uninfected, based on prion protein affinity ligands that we selected by high-through-put screening of combinatorial ligand libraries. Those ligands that performed best were tested for their ability to remove TSE infectivity using animal bioassays. By spiking human red blood cells with brain-derived preparations of TSE infectivity, we were able to show that the capacity of the resins far exceeded the mass of prion protein expected for a single 500ml unit of blood. By challenging the resins with whole blood collected from rodents during symptomatic infection with TSE, we demonstrated removal of relevant, blood-associated infectivity to the limit of detection. Several of these ligands are now being developed into devices for removing TSE infectivity from red blood cells collected for transfusion, and for removal of TSE infectivity from plasma derivatives prepared as human therapeutics.
 

Industrial and Engineering Chemistry Divisional Fellow Award Symposium - Dr. Ruben Carbonell
1:30 PM-4:50 PM, Monday, April 7, 2008 Morial Convention Center -- Rm. 231, Oral

Division of Industrial & Engineering Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008