Advancing Prion Science Guidance for the National Prion Research Program: Interim Report (2003) / Chapter Skim
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2. Prion Diseases and Their Challenges
2. Prion Diseases and Their Challenges
Pages 23-40
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From page 23... ...
The tribe called the illness kuru, meaning "to tremble" or "to shiver." Studies of the brains of deceased patients revealed widespread neurodegeneration marked by vacuoles in the cytoplasms of nerve cells (Klatzo et al., 1959~. The vacuoles gave the victims' brains a sponge-like appearance at the microscopic level, hence the term "spongiform encephalopathy." Ethnological and epidemiological studies indicated that kuru was transmitted during an endocannibalistic~ funeral ritual (Alpers, 1968; Gajdusek, 1977; Glasse, 1967~.
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290~. On the basis of these observations, Hadlow suggested that experimental transmission of kuru into nonhuman primates might prove fruitful, since veterinary scientists were successfully investigating scrapie by inoculating healthy sheep and goats with brain tissue from animals with scrapie.
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None of these explanations gained widespread acceptance, however, and the cause of scrapie remained an enigma. In 1982, neurologist Stanley Prusiner asserted that the infectious agent in scrapie was either a protein or a small nucleic acid surrounded by a tightly packed protein (Prusiner, 1982, 1999~.
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THE NATURE OF PRIONS AND PRION DISEASES The protein that platers a critical role in prion disease is called PrP and is encoded by the gene PROP on chromosome 20 in humans. Like all proteins, PrP has a characteristic conformation, but under certain conditions it folds into an abnormal shape that is associated with fatal neurodegeneration after a long incubation period.
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Do en =N C-)
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The misfolded proteins aggregate into rodshaped fibrils, and prions at the ends of the rods continue converting normal PrP into PrPSc (Caughey, 2002~. By an unknown mechanism, the aggregated prions appear to destroy nerve cells and create microscopic vacuoles in the brain.
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THE EPIDEMIC OF BOVINE SPONGIFORM ENCEPHALOPATHY AND THE EMERGENCE OF vCJD Prion diseases remained obscure outside the circles of infectious disease specialists and neurologists until the mad cow epidemic struck in the United Kingdom. The illness was first recognized in 1985 when a handful of cattle from disparate locations in the United Kingdom began dying of a strange illness marked by insidious onset, rapidly progressive dementia, and death (Wells et al., 1987; Wilesmith et al., 19881.
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Many other countries worldwide unknowingly imported BSE-infected cattle and contaminated meat and bonemeal from the United Kingdom and have also suffered outbreaks of BSE, public panic, financial losses, and political repercussions. The Risk of BSE in the United States Two recent reports suggest that the federal government should strengthen its policies designed to avert BSE and vCJD, although the first study concluded that the risks of a BSE outbreak in the United States are minimal (GAO, 2002; Harvard Center for Risk Analysis, Harvard School of Public Health, Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University, 2001~.
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Sick animals became listless, depressed, and anorexic and died of emaciation, secondary complications, or euthanasia within 2 weeks to 8 months after the onset of clinical symptoms. The nature of these signs led biologists to name the illness "chronic wasting disease."
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By contrast, some researchers speculate that CWD in farmed animals has spread more widely and unpredictably due to market forces (Williams and Miller, 2002~. Unique Challenges in Conducting Prion Research Much about prion diseases remains unclear: how prions replicate, why they target neurons, and how prions kill neurons are a few examples.
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Given that there are few tools to inactivate priors, the ability to test blood and other tissues for prions would help prevent the inadvertent transmission of vCJD by blood transfusion or organ transplantation, provided that there is actually any infectious agent to be detected in blood or the organs used for transplantation. Despite many attempts in Europe and the United States, no one has developed a reliable antemortem diagnostic test for TSEs.
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1999. Prion protein and the transmissible spongiform encephalopathy diseases.
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Lancet ii:289-290. Harvard Center for Risk Analysis, Harvard School of Public Health, Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University.
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2000. Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: role of prion protein expression in peripheral nerves and spleen.
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2002. Chronic wasting disease in deer and elk in North America.
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