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Preface
Executive Summary
- Conference Proceedings
- Invitational Research Planning Workshop
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In the last two decades of the twentieth century, the staggering impact of the prion disease bovine spongiform encephalopathy (BSE) on human and animal health and economics was felt in the United Kingdom. Recognizing that the potential implications of BSE were a concern to Canadian health and economics as well, Health Canada held several meetings to discuss prion diseases. The meetings underscored the necessity of developing a long-term plan in Canada to address the health, economic, and research challenges posed by these diseases. This conference was born out of that necessity.
Meeting the Challenge of Prion Diseases was initially planned for the fall of 2001. The attacks on the World Trade Center and Pentagon, and the subsequent anthrax poisonings in the United States, however, had the conference organizers scrambling to address what had suddenly become a more pressing issue: bioterrorism and the diseases it potentially could unleash. Rescheduled for April 2003 in Toronto, the conference next fell victim to Nature's own brand of bioterrorism as the SARS epidemic struck the Greater Toronto Area, and the World Health Organization issued a travel advisory against the city. The conference was once again postponed; yet the urgent need to address prion diseases and their impact was dramatically emphasized just one month later in May 2003, when Canada's first case of BSE was identified. Unfortunately, these delays meant that when the first BSE cow was identified in Alberta, we still had no long-term plan in place to deal with it.
Bringing together scientists, students and health workers from universities, institutes and governments in Canada, the United States and Europe, the conference was finally held in Edmonton, Alberta, on Thursday, September 25 and Friday, September 26, 2003.
Following the research conference, a working group met on Saturday, September 27, to determine how to enhance Canadian research opportunities and results related to prions and prion diseases. The conference program was planned to address research across four themes: biomedical, clinical, health services and systems, and the health of populations as it is affected by societal, cultural and environmental influences.
The results of the conference and working group are contained in this report. Important areas of research and capacity building have been identified, and plans to address them have been put in place. The need remains to follow up on these plans; yet the current ability to do so is minimal, as we still do not have a Canadian capacity to address prion disease in terms of diagnostics, surveillance, monitoring therapy, and treatment. With only one biocontainment level four facility in Winnipeg and relatively few level three facilities across the country, we lack sufficient infrastructure to do the work. We need to build capacity and bring people into it, but we also need to build the facilities. We cannot do it without the people, and we cannot do it without the facilities. It remains to be decided how we will sustain such facilities once the immediate threat is diminished.
While prion disease and its implications fall within the mandate of the CIHR, they are also within the Canadian government's mandate regarding human health, economic development, and innovation. Indeed, all stakeholders and policy makers should consider this an area of urgent need to address. Both public and private sectors should be working hand in hand to give the financial support and to do the research. We must put policies in place so we are ready for the future, and these policies should be based on scientific evidence. The purpose of the conference and its ensuing report, therefore, is to inform how that policy can be developed and implemented based on science. The federal and provincial governments plus the private sector all share the responsibility to put this together.
Fortunately, our policy makers have been listening to our needs. In the time it has taken to prepare this report since the conference was held in September 2003, the federal government tabled its new budget, and based on information made available through this meeting and other sources, has committed an additional $5 million a year through the Networks of Centres of Excellence program to support research on BSE and other TSEs. It is a step in the right direction to follow up on our plans, build the capacity and infrastructure we need, and secure a position for Canada as a forerunner in prions research.
The success of any enterprise depends on the efforts of the people involved in its planning, implementation and follow-up. I would like to thank the following groups and individuals for their contributions to the Meeting the Challenge of Prion Diseases Conference and Invitational Planning Workshop, and the preparation of this report. We are extremely grateful for their expertise and assistance.
The Canadian Institutes of Health Research Institute of Infection and Immunity (CIHR-III), in partnership with the CIHR Institute of Population and Public Health and Health Canada, sponsored Meeting the Challenge of Prion Diseases, an international research conference, in Edmonton, Alberta, at the Fairmont Hotel Macdonald on Thursday, September 25 and Friday, September 26, 2003. The conference brought together scientists, students, and health workers from universities, institutes, and governments in Canada, the United States, and Europe. Following the research conference, a working group met on Saturday, September 27, to determine how to enhance Canadian research opportunities and results related to prions and prion diseases.
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of fatal neurological diseases of humans and animals characterized by deterioration of the central nervous system which causes vacuoles (sponge-like holes) in the brain. Human variants include Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Sträussler-Scheinker disease (GSS), and Kuru. Prion diseases in animals consist of bovine spongiform encephalopathy (BSE), chronic wasting disease in deer and elk, feline spongiform encephalopathy, scrapie in sheep, and transmissible mink encephalopathy (TME).
Dr. Bhagirath Singh, Scientific Director for the CIHR Institute of Infection and Immunity, related CIHR's mandate-to identify and study diseases and their impact on human health-to the conference's four main goals: 1) to identify research questions and health challenges of prions, 2) to determine key areas for interdisciplinary prion research, 3) to foster new research efforts and opportunities in prion diseases in Canada and internationally, and 4) to lay the background for a working group to discuss possible courses to establish a Canadian research agenda for prion diseases.
Session I: Prions and Prion Diseases
Chair: Dr. Neil Cashman, Centre for Research in Neurodegenerative Diseases, Toronto, Canada
The speakers in Session I provided a compendium of Prions and Prion Diseases, looking at their history and development, phenotypes and phenomenology, pathology, and genetics in human and animal populations. Dr. Paul Brown from the National Institutes of Health, USA, presented the keynote address, Prions and Prion Diseases: An Overview. He explained the history of prion studies beginning with scrapie, which was well established and identifiable as an infectious disease in Europe by 1756, up to the present. Dr. Richard Knight, of the CJD Surveillance Unit, Edinburgh, United Kingdom, spoke on Prion Diseases: Phenotypes and Phenomenology, describing the phenotypes and phenomenology of prion diseases, focusing mainly on the four types of CJD, sporadic, genetic, iatrogenic and variant. Dr. Herbert Budka, University of Vienna, Vienna, Austria, discussed the Pathology of Human Prion Diseases, noting the importance of neuropathology in both the surveillance and research on prion diseases. Dr. Maura Ricketts, Health Canada, chaired the final presentation in Session I, in which Dr. Michael Coulthart, also from Health Canada, presented Genetics of Prion Diseases: Overview and Comparative Perspectives. He gave a summary of the genetics of human prion diseases and presented the results from the Canadian BSE case.
Session II: Prions and Public Health
Chair: Dr. Michael Coulthart, Chief, National Laboratory for Prion Diseases, Health Canada
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In Session II, the speakers focused on Prions and their relationship to Public Health, investigating such issues as emerging animal prion diseases, the epidemiology, transmission, and immunobiology of prion diseases, and the Canadian BSE case and the policy framework surrounding it. Dr. Ray Bradley, CBE, BSE Consultant, United Kingdom, discussed Emerging Animal Prion Diseases. Dr. Bradley defined the term emerging disease, and applied his definition against the major animal TSEs in chronological order of their discovery and appraised the risk to humans for each of the diseases. Dr. Maura Ricketts, Health Canada, spoke about the Epidemiology and Risk Factors of Prion Diseases, discussing the epidemiology of BSE from the perspective of public health policy, focusing on two important routes of transmission, food and vaccines, to illustrate the complexity of the problems that they present. Dr. Paul Brown, National Institutes of Health, USA, addressed issues surrounding the Iatrogenic Transmission of Prion Diseases, Including Blood, noting that the iatrogenic potential of blood is minimized by the fact that it is an inefficient route. No cases of CJD in a recipient of a blood product or a blood component have yet been identified. Dr. Ron Rogers of Health Canada presented information on The Canadian BSE Case and Public Health, outlining the steps taken in the identification of Canada's 2003 BSE case and government response to it. The Policy Framework and Transparency in Relation to Human TSEs was presented by Dr. Paul Gully from Health Canada. Dr. Gully described Health Canada's purpose and strategic plan, noting that its decision-making framework is a collaborative process by decision makers involving all interested and affected parties.
Session III: New Challenges of a Protein-Only Agent
Chair: Dr. Maura Ricketts, Senior Medical Advisor, Blood Safety Surveillance and Health Care Acquired Infections Division, Health Canada
Session III gave consideration to New Challenges of a Protein-Only Agent, examining the possibilities for rapid diagnosis of BSE, prion decontamination, and prion research infrastructure. Dr. Jean-Philippe Deslys of the Atomic Energy Commission, France, spoke about Rapid Diagnosis of BSE. His studies evaluating the "Biorad" BSE assay found that this test was 10 to 30 times more sensitive than the other three BSE assays. Dr. David Taylor, Institute for Animal Health Neuropathogenesis Unit, Edinburgh, United Kingdom, discussed Prion Decontamination, addressing the inherent problems in finding effective means to inactivate the infectious agents that cause transmissible spongiform encephalopathies. Dr. Robert Rohwer from the Veterans Administration Medical Center, Maryland, USA, presented issues surrounding Prion Research Infrastructure, noting that TSE research requires biocontainment level 3 (BL3) facilities designed for animal studies equipped with state-of-the-art instrumentation, access to reagents and materials, and researchers and staff with TSE expertise.
Session IV: Prion Science And Health
Chair: Dr. Antonio Giulivi, Director, Blood Safety and Health Care Acquired Infections Division, Health Canada
In Session IV, Prion Science and Health was discussed. The morning session consisted of four presentations. Dr. Inga Zerr, CJD Surveillance, Neurologische Klinik, Universitatskilikum Gottingen, Germany, provided information on the Diagnosis of Prion Diseases, explaining the differences in clinical features between variant and sporadic CJD. Dr. Byron Caughey, National Institutes of Health, USA, spoke about the Treatment of Prion Diseases, describing studies in which he performed high throughput screening of a library of 2,000 small molecular weight compounds for inhibitory properties of PrP conversion from a protease sensitive to a protease resistant state using the RML and 22L strains. Dr. Neil Mabbott, Institute for Animal Health, Edinburgh, United Kingdom, presented Immunobiology of Prions 1: Cells. Dr. Mabbott has demonstrated that follicular dendritic cells are important for the early accumulation of prions in lymphatic tissue in a mouse model of scrapie disease. Dr. Neil Cashman, University of Toronto, Canada, continued the discussion of the Immunobiology of Prions with a related presentation on Antibodies. Dr. Cashman's studies indicate that YYR motifs may be ideal therapeutic and diagnostic targets, and antibodies directed against this motif may be an ideal therapeutic.
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In the afternoon, five talks were presented. Dr. David Westaway, University of Toronto, Canada, discussed The Prion Protein Homolog Doppel. The results of his studies question some of the currently held views that Dpl and PrP interact with proteins outside of the cell. Dr. Andrea Leblanc from McGill University, Canada, addressed issues surrounding Prions and Apoptosis. Dr. Leblanc showed that the normal PrP protein provides a protective effect to neurons when they come under oxidative stress or when the cell death inducing protein Bax is present. Dr. Witold K. Surewicz, Case Western Reserve University, Ohio, USA, discussed the Biophysics of Prion Proteins and explained the folding properties of prion proteins. Dr. Catherine Bergeron, from the University of Toronto, presented on Lesion Profiling, noting that examination of the lesions in various sections of the brain showed that lesion profiling alone cannot predict the molecular phenotype of CJD though four groups could be recognized, Type 1, Type 2, MM2, and vCJD, and lesion profiling could reliably identify new prion strains. In the last presentation of the conference, Dr. Surachai Supattapone, Dartmouth Medical School, Hanover, New Hampshire, USA, discussed Host Factors Required for Amplification of Protease-resistant PrP Molecules in vitro. Dr. Supattapone was able to amplify PrPSc greater than 10 fold from a mixture of PrPSc and PrPC proteins. He further showed that the amplification is prion strain specific and is dependent on time, temperature and free thiol groups. Interestingly, Dr. Supattapone identified that the process of amplification requires additional cell factors, namely RNA.
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Following the research conference, a working group met on Saturday, September 27, to determine how to enhance Canadian research opportunities and results related to prions and prion diseases. The consultation's objectives were to summarize key learnings and implications of the conference for future Canadian research; develop draft recommendations on five or six priority strategic research themes for Canadian researchers over the next 10 years; identify opportunities to build capacity through supportive infrastructures; and enhance linkages and interactions among participants.
For the purpose of this workshop, strategic research themes were defined as prions-related research areas and applications central to the reduction of the burden of these diseases in Canada. Research themes were required to meet the following criteria:
Volunteer leaders each focused on one of four questions to stimulate the plenary session. Dr. Kumanan Wilson led a discussion based on the question, What international research priorities are currently in place? Replies included the need for biomedical research into prion diseases, capacity building, knowledge translation and communication, agricultural and wildlife research and economic impact of prion diseases. Dr. Paul Gully's presentation focused on the question, What are the major health challenges of prion diseases? He emphasized that the overall challenge is to educate politicians and the public that although epidemics may occur that we cannot prevent, the expertise must be in place to respond when they happen. Prion stakeholders need to be where policy is being made to have an impact on decision making. Investigating the question, What are the major unanswered questions in the basic science of prion diseases, Dr. Neil Cashman's presentation elicited a lively discussion on a number of contentious issues that are related to prion basic science, including the nature of the prion hypothesis in general, whether there is a need to continue research into defining the infectious protein, and whether focusing on prions may be too narrow an approach as they may be part of a broader range of misfolding proteins or connected to viral agents. Consideration of the final question, What are Canada's strengths and gaps (opportunities) in relation to research on prion diseases, was led by Dr. Michael Coulthart, who opened discussion in this area with his description of a three-part focus on approach, issues and assets.
From these discussions, priority research themes and capacity building priorities, as well as strategies with which to deal with them, were established. The participants agreed that the following research themes (alphabetical order) merited investigation: applied CWD pathogenesis; ecology (the relationship of humans to prions and the environment); testing methods; infectivity, prevention and treatment of prion diseases; rendering and decontamination research in various settings such as hospitals and farms; and risk assessment, communication and socio-economic impact, including public health policy and impact. Identified capacity building priorities included the creation of a national virtual network or institute for laboratories or people; the development of a Canadian Prions Institute that contains a common P3 facility or training centre; support for recruiting and maintaining highly qualified personnel for lab support; and the creation of a virtual interdisciplinary forum to facilitate comprehensive and integrated approaches to issues such as policy. The participants suggested the following strategies for implementing these research themes and capacity building: i) build on Canada's neuroscience capacity; ii) create funded exchange programs with other countries; iii) provide more longer-term funding for basic research; and iv) develop a mechanism for applying for peer-reviewed funding and infrastructure.
© Her Majesty the Queen in Right of Canada (2004)
Cat. No.: MR21-52/2004-1
ISBN 0-662-68487-7
