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15 May 2004 08:30:00 Est - Updated
Contact: Stephen M. Apatow  (203) 668-0282

Research indicates mad cow pathogen can cause both sporadic or classical Creutzfeldt-Jakob (CJD) disease and variant form.

May 7 (HRI) - The scientific paper "BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein," published in the issue of the EMBO Journal, Vol. 21, No. 23, 6358-6368, 2002 presented a new challenge to international public health: 

Abstract: Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrP\Sc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure. 

In a second paper entitled "Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease," Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0305777101: 

Abstract: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrPSc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called "species barrier" between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrPSc accumulation. In addition, Western blot analysis showed a PrPSc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPSc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease. 

In response to this research, the World Organization for Animal Health (OIE), Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO) are being asked to clearly re-define the risk of exposure to the BSE agent, in the context of sporadic or classical CJD. 

FAO estimates that between 1986-96 up to today, meat and bone meal (MBM) from Europe was exported to more than 100 countries. Around 100 countries imported live cattle. Some countries also re-exported MBM to third countries. All countries which have imported cattle or meat and bone meal that originated from Western Europe, during and since the 1980s, can be therefore considered at risk from the disease. Regions that have imported sizeable quantities of meat meal from the UK during and since the 1980s include the Near East, Eastern Europe and Asia. 

The UPI report "Mad Cow: Linked to thousands of CJD cases?" emphasized: 

-- "Now people are beginning to realize that because something looks like sporadic CJD they can't necessarily conclude that it's not linked to (mad cow disease)," said Laura Manuelidis, section chief of surgery in the neuropathology department at Yale University, who conducted a 1989 study that found 13 percent of Alzheimer's patients actually had CJD. 
-- Several studies, including the one by Manuelidis, have found autopsies reveal 3-percent-to-13-percent of patients diagnosed with Alzheimer's or dementia actually suffered from CJD. Those numbers might sound low, but there are 4-million Alzheimer's cases and hundreds of thousands of dementia cases in the United States. A small percentage of those cases could add up to 120,000 or more CJD victims going undetected and not included in official statistics. 
-- At the same time autopsies have been declining, the number of deaths attributed to Alzheimer's has increased more than 50-fold since 1979, going from 857 deaths then to nearly 50,000 in 2000. Though it is unlikely the dramatic increase in Alzheimer's is due entirely to misdiagnosed CJD cases, it "could explain some of the increase we've seen," Manuelidis said. 
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Stephen M. Apatow, President and Director of Research and Development, of the nonprofit organization Humanitarian Resource Institute, is a specialist in strategic planning and project development of initiatives associated with human medicine, veterinary medicine and U.S. and international law. Current programs include the internet based Biodefense Reference Library, Foreign Animal and Zoonotic Disease Center, Bioinformatics: Pathobiological Diagnostics Center and Biodefense Legal Reference Library. To enhance collaboration between Humanitarian Resource Institute and the international community of scholars, the Humanitarian University Consortium was formed to enhance the development of initiatives associated with economic, social, cultural and humanitarian issues worldwide.