Abstract
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, describe a group of fatal neurodegenerative disorders affecting both humans and animals. Accumulation of misfolded prion proteins is the pathological hallmark of these disorders; such accumulation occurs in lymphoreticular tissue prior to CNS involvement in scrapie, experimental models and human variant Creutzfeldt–Jakob disease. Lymphoreticular accumulation of misfolded prion protein has not been demonstrated in human sporadic or genetic forms of TSE. Once clinical symptoms develop, all prion disorders have a rapidly progressive and lethal course, and no effective therapy exists. In the past 10 years, antibody-based immunotherapy has been considered for other neurodegenerative disorders associated with protein misfolding and, therefore, might also be an effective approach to prevention or treatment of prion disease. Self-tolerance to endogenous prion protein is, however, a major challenge to the development of effective immunotherapy, as is the risk of adverse effects from active immunization. This Review summarizes the evidence that immunization could slow disease progression or increase lifespan in animal models of prion diseases. The therapeutic potential of these strategies in treating patients with prion diseases is also discussed.
Key Points
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Prion diseases are lethal neurodegenerative disorders for which no effective therapy is currently available
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Identification of an appropriate prion epitope and circumvention of self-tolerance are major obstacles to inducing a therapeutic immune response
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Potential therapeutic approaches include active and passive immunization strategies involving endogenous or synthetic prion proteins
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Promising results for both active and passive immunization strategies have been reported in animal models of prion diseases
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Active immunization against prion proteins can induce an inflammatory response in the brain; passive immunization might, therefore, be a safer approach
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Acknowledgements
This work was supported by a research grant of the University Medical Center Giessen and Marburg. Y. Roettger received a research grant from the Competence network Degenerative Dementias, funded by the German Ministry of Education and Research (BMBF, 01GI1008C). The article was edited for language errors by editors from American Journal Experts.
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Y. Roettger, J.-P. Bach and R. Dodel researched the data for the article. Y. Roettger, Y. Du, M. Bacher, I. Zerr, R. Dodel and J.-P. Bach provided substantial contributions to discussion of the content, review and/or editing of the manuscript before submission. Y. Roettger and J.-P. Bach wrote the article.
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M. Bacher, R. Dodel and J.-P. Bach hold patent applications 20090028869 and 2366714 A1. J.-P. Bach has received research grants from Grifols and Baxter. In addition, he has received lecturing fees from Teva Pharmaceuticals. The other authors declare no competing interests.
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Roettger, Y., Du, Y., Bacher, M. et al. Immunotherapy in prion disease. Nat Rev Neurol 9, 98–105 (2013). https://doi.org/10.1038/nrneurol.2012.258
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DOI: https://doi.org/10.1038/nrneurol.2012.258
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