Prion Reduction

Leukotrap® Affinity Plus Prion and Leucocyte Reduction Filter System 

Leukotrap® Affinity Plus Prion and Leucocyte Reduction Filter System is CE marked under the Medical Devices Directive (93/42/EEC)  

Leukotrap® Affinity Plus Prion and Leucocyte Reduction Filter

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The Leukotrap® Affinity Plus Prion and Leucocyte Reduction Filter System is Not Currently Available for Sale in the U.S. or Canada 

The term “Prion” stands for “proteinaceous infectious particle”. Prions are not inactivated or destroyed by procedures that modify nucleic acids¹. The normal cellular form, which is found in different tissues and organs in the body, is designated PrPc and contains mainly alpha helix (about 42%) with little beta sheet protein structure (about 3%). The normal forms are soluble in detergent, mainly monomeric, do not exist as aggregates, and can be digested by an enzyme called proteinase K. In contrast, the abnormal prion, designated PrPSc, is rich in beta sheet (43%), is partially resistant to digestion by proteinase K, not soluble in detergent and tends to form aggregates or polymeric structures¹. Unlike viruses, bacteria, fungi and parasites, prions do not contain deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). In contrast to viruses, prions are nonimmunogenic. They do not elicit an immune response because the host has been rendered tolerant to PrPSc by PrPc². Prions reproduce by recruiting the normal cellular isoform and stimulating its conversion into the disease-causing isoform, PrPSc^2,3. 

1 Prusiner SB. Science 1982;216:136-144.
2 Prusiner SB. Scic Am, 2004; 86-93.
3 Prusiner SB. Proc Natl Acad Sci, USA 1998;95:13363-13383.

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that affect both humans and animals. The diseases include: scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle (commonly called mad cow disease) and Creutzfeldt-Jakob disease (CJD) and its variant form (vCJD) in humans. The hallmark of prion diseases is the accumulation of abnormal prions in the central nervous system. The disease is characterized neuropathologically by the presence of numerous deposits or plaques known as amyloid proteins or “florid plaques” and vacuoles or holes in areas of the brain such as the cerebellum and cerebrum^4,5. The pathogen responsible for the transmission of vCJD and all TSEs is believed to be abnormal prion⁶. 

4 Prusiner SB et al. Proc Natl Acad Sci 90:10608-10612. 
5 Centers for Disease Control and Prevention, USA, Update 2002: Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease. 
6 Prusiner SB. Science 1982;216:136-144.

The variant form of CJD (vCJD) is the human equivalent of BSE and is believed to be caused by the consumption of meat products contaminated with BSE. vCJD is different from the classical form of CJD. For example, the median age at death of patients with classic CJD is 68 years, and very few cases occur in persons under 30 years of age. In contrast, the median age at death of patients with vCJD in the United Kingdom is 28 years. vCJD predominantly affects younger people and has atypical clinical features, with prominent psychiatric (such as anxiety, insomnia or withdrawal) or sensory symptoms at the time of clinical manifestation of the disease^2,6,7,8.  In vCJD, PrPSc builds up not just in the brain but also in the lymphoid system, such as tonsils and appendix, suggesting that PrPSc enters the blood stream at some point. To date, 216 vCJD cases and deaths in people have been confirmed worldwide in 11 countries with most of the cases (170) occurring in the United Kingdom⁹.  Regular updates on numbers of reported cases are available under http://www.cjd.ed.ac.uk/vcjdworld.htm. 

2 Prusiner SB. Scic Am, 2004; 86-93.
6 Hill AF et al. Lancet 1997;349:99-100.
7 Hill AF et al. Lancet 1999;353:183-189.
8 Ironside et al. Lancet 2000;355:1693-1694.
9 CJD Statistics: CJD Surveillance unit, Edinburgh. Update, October 2009 http://www.cjd.ed.ac.uk/vcjdworld.htm.

Yes, animal studies have shown that infectious prions can be transmitted to healthy animals through transfusions from infected animals^{10,11,12, 13}. More recently, four cases of human transmission of vCJD through transfusion of blood components from asymptomatic donor who subsequently developed the disease were reported^14,15,16, dispelling any lingering doubts about blood infectivity in humans with vCJD.

10 Houston et al. Lancet 2000; 356: 999-1000.
11 Houston et all, Blood 2008, 112, 4739-4745.
12 Hunter et al. J Gen Virol 2002; 83: 2897-2905.
13 Bons et al. Transfusion 2002; 42:513-516.
14 Llewelyn et al. Lancet 2004;363:417-421.
15 Peden et al. Lancet 2004;364:527-529.
16 United Kingdom Health Protection Agency (HPA) (CJD and blood; updated 21st of January 2009, http//www.hpa.org.uk/infectious/topics_az/cjd/,menu.htm

To prevent the spread of BSE, severe restrictions have been placed on the importation of live ruminants such as cattle, sheep and goats, and certain ruminant products from countries where BSE is known to exist. In many European countries, public health control measures, including elimination of sick animals, bans on specified risk materials, and increased BSE surveillance, are aimed at preventing contamination of the human food chains. vCJD transmission risk via blood transfusion is being minimized by a number of measures including a ban on blood donation from people who lived for three months or more in the UK between 1980 and 1996. Universal leukocyte reduction was introduced in the UK as a preventive measure to reduce the risk of transmission of vCJD through blood transfusion^{17, 18}. However, recent reports from animal studies suggest that leukocyte reduction is only about 42% effective in reducing the risk of transmission of infectious prion, since not all prions found in the blood are cell-associated¹⁹. Pall Medical is addressing the issue of the potential for transfusion transmission of infectious prions with an innovative proprietary technology.

The novel Pall Leukotrap Affinity Plus Prion and Leucocyte Reduction filter reduces leukocytes and infectious prions—both free and cell associated. 

The reduction of prion proteins in blood components is a significant advance toward safer transfusions.  Blood Safety Measures that include: appropriate donor deferral and selective blood screening for known pathogens combined with leukoreduction and prion reduction represent a new blood safety paradigm vital to protecting transfusion recipients from infectious threats.

17 United Kingdom Spongiform Encephalopathy Advisory Committee (SEAC) Annual Report 1997-1998, pp10; Department of Environment, Food and Rural Affairs, London, England, UK
18 Murphy et al, Transfus Med Rev 1999; 13; 75-83
19 Gregori et al, Lancet 2004; 364; 529-531

Most of the methods that are used to kill or inactivate pathogens in blood and blood components are not effective against infectious prions. These methods target nucleic acid components of the pathogens such as deoxyribonucleic acid and ribonucleic acid (DNA or RNA). Since prions lack nucleic acids, they are not inactivated by these technologies.