Advancing Prion Science Guidance for the National Prion Research Program (2004) / Chapter Skim
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Pages 5-32
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From page 5... ...
Yet, unlike all other known infectious diseases, TSE infectivity appears to be associated with an abnormally folded protein known as a prion (Prusiner, 19821. There is no cure, prophylaxis, or fail-safe antemortem diagnostic test for TSEs, often called prion diseases.
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From page 6... ...
The origin of vCJD in prior-infected cattle raises the concern that chronic wasting disease (CWD) , a prion disease spreading among North American deer and elk (Williams and Miller, 2002)
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From page 7... ...
The members of the committee were asked to examine novel technologies that might advance diagnostics; evaluate the reagents and assays used in prion research and recommend improvements; evaluate the adequacy of the TSE research infrastructure in the United States with respect to the number of investigators, physical facilities, and training needs; suggest opportunities for collaboration with foreign investigators; evaluate the threat of TSEs to U.S. military forces with respect to their food supply, their blood supply, and any other factors; provide advice on public health policies or surveillance programs that require new research or that might affect the military; and recommend additional research on ways to reduce or prevent TSEs.
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From page 8... ...
PrPreS is an abnormally folded prion protein that is highly resistant to digestion by the enzyme proteinase K (PK) and is strongly associated with prion disease.
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From page 9... ...
Current gaps in knowledge of the pathogenesis of prion diseases prevent better characterization of diagnostic targets and strategies. The routes of transmission, the factors that influence host susceptibility, the lack of an immune response, the mechanisms of neuroinvasion, and the cause or causes of cellular toxicity all lack satisfactory explanations; filling these gaps would result in tests with greater sensitivity and specificity.
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From page 10... ...
TSE DL\GNOSllCS Obstacles to Developing Antemortem Diagnostics for TSEs Conventional methods used to diagnose most infectious diseases, such as malaria, tuberculosis, hepatitis, and AIDS, fail to detect prion diseases for numerous reasons. First, a prion is a host protein with an altered conformation such that the immune system does not recognize it as foreign and does not produce antibodies against it.
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From page 11... ...
Moreover, the sensitivity of these tests must still be improved by several orders of magnitude if they are to reliably detect an infectious unit of priors. Recommendation 4.1: Fund research to clevelop new assays most likely to achieve quantum leaps in the quality of prion detection tools, rather than incremental improvements to existing tests.
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From page 12... ...
, and the committee recommends that it be applied to TSEs. Recommendation 4.4: Fund research to identify surrogate markers or signatures for the detection of prions or prion diseases.
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From page 13... ...
By contrast, investigations into the transmissibility of the vCTD agent through blood transfusion are just beginning to gain momentum. Because a significant amount of prions appears in the lymphoreticular system in vCTD cases but not in other varieties of human TSEs, the blood of vCTD-infected individuals may contain priors.
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From page 14... ...
, even though there has never been a reported case of BSE in the United States. Human TSEs are reportable in 12 states.
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From page 15... ...
In particular, support research to identify potential cases of variant Creutzfel~t-lakob disease and new human TSEs possibly caused by the agent of chronic wasting disease. Surveillance for TSEs in Animals Chronic Wasting Disease Although CWD has existed in deer and elk in Colorado and Wyoming since at least the 1960s (Miller et al., 2000; Williams and Young, 1980)
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From page 16... ...
Recommendation 6.3: Provide funds to support the development of a nationwide surveillance system for chronic wasting disease in the United States. Bovine Spongiform Encephalopathy and Scrapie USDA runs surveillance programs for the other two animal TSEs of concern in this country: BSE and scrapie.
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From page 17... ...
residents from possible exposure to TSE agents in food and other products that come partially or completely from potential carriers of TSE agents. Policies to Prevent the Entry and Spread of BSE The United States applies the above formula primarily to the infectious agent of BSE through four policies: the import ban, the feed ban, slaughter surveillance, and the ban on central nervous system (CNS)
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The poorly understood risks of the CWD agent should be characterized scientifically. Recommendation 7.2: Fund risk assessments that characterize the exposure of hunters, cervid processing establishments, and consumers to the infectious agent of chronic wasting disease.
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In contrast to blood, blood products, and blood derivatives, certain human tissues and hormones have been documental to transmit TSE agents from an infected human donor to a healthy human recipient. Present FDA regulations and guidance to industry have reduced the rate of this form of TSE transmission in the United States.
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Recommendation 7.5: Fund research to develop standard test methods for detecting prion contamination in environmental samples. The longevity of TSE infectivity specifically in soil has tremendous implications for the proper disposal of animals infected with a TSE agent and for these animals offal and rendered material.
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From page 21... ...
Given that the United Kingdom and Europe need such methods urgently, this area of research appears ripe for international collaboration. Recommendation 7.6: Fund research to identify safe, cost-effective disposal mechanisms for animals and rendered waste infected with agents of transmissible spongiform encephalopathies.
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From page 22... ...
Recommendation 7.7: Fund research to develop new therapeutic agents, including antibodies, that either block the conversion of prpc to PrPSc or disrupt the molecular mechanisms of pathogenesis of transmissible spongiform encephalopathies after this conversion has taken place. The most promising approach appears to be rational drug design, which begins with knowledge of the tertiary structure of the protein or molecule that the therapeutic agent will target.
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From page 23... ...
, and by building new ones. Recommendation 8.3: Provide funds to develop scientifically based biological safety level standards for laboratories conducting research that involves infectious agents known to cause transmissible spongiform encephalopathies.
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Recommendation 8.6: Provide funds to enable U.S.-based investigators of transmissible spongiform encephalopathies (TSEs) to collaborate or train with TSE investigators internationally and to use TSE research facilities abroad.
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Department of Defense and the Department of Veterans Affairs. CONCLUSION This final report of the IOM Committee on Transmissible Spongiform Encephalopathies: Assessment of Relevant Science provides an unprecedented overview of the ways in which TSEs impact human and animal health from donated blood to deer hunting.
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the mechanisms of pathogenesis of transmissible spongiform encephalopathies (4) the physiological function of prpC Improving Diagnostics Fund research to: 1 4.1 Develop new assays most likely to achieve quantum leaps in the quality of prion detection tools, rather than incremental improvements to existing tests.
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From page 27... ...
6.4 Expand research on the natural history, prevalence, distribution, exposure and transmission characteristics, host susceptibility, and host range of transmissible spongiform encephalopathies, especially chronic wasting disease. Assessment of Strategies to Prevent and Treat TSEs 7.1 Fund research to improve rapid, accurate, and affordable screening assays for central nervous system (CNS)
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From page 28... ...
Provide funds to: 8.3 Develop scientifically based biological safety level standards for laboratories conducting research that involves infectious agents known to cause transmissible spongiform encephalopathies. 8.4 Support new or established transmissible spongiform encephalopathy (TSE)
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From page 29... ...
to collaborate or train with TSE investigators internationally and to use TSE research facilities abroad. Exploiting such opportunities will expand the range of TSE research that U.S.
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From page 30... ...
2003. National chronic wasting disease surveillance in free-ranging cervids: accomplishments and needs.
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From page 31... ...
2000. Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming.
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From page 32... ...
1980. Chronic wasting disease of captive mule deer: a spongiform encephalopathy.
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