Objective
The significance of the clinico-pathological variants of Creutzfeldt-Jakob disease, including the new variant recently described in the United Kingdom andalso reported in France, is still being debated. The hypothesis that they might be due to different strains has been repeatedly raised. Validation of this hypothesis would require rodent models sensitive to human prions. These models would make it possible to distinguish strains of human prions with different patterns of incubation periods and lesion profiles. However, inoculation of rodents usually gives variable and irregular results, depending on species and strains. The use of transgenic mice highly susceptible to human agents is a solution. However, their transmission characteristics are not precisely known, however. The infectivity of human prion diseases has been studied largely with apes and monkeys, which are considered today as the gold standard. This model, however, has a number of pitfalls.
We plan to study transgenic mice expressing human prion protein in order to:
1) Study and compare the experimental diseases produced by inoculation of brain extracts from various forms of Creutzfeldt-Jakob disease (sporadic, new variant, genetic and infectious);
2) Assess their susceptibility to sporadic Creutzfeldt-Jakob disease and to the new variant of Creutzfeldt-Jakob disease by comparing them with the monkey model. This study will test the strain hypothesis for the clinico-pathological variants of Creutzfeldt-Jakob disease, including the new variant of Creutzfeldt-Jakob disease. This may be of major pathogenetic and epidemiological relevance. In addition, it will validate a sensitive tool for the assessment of the infectivity of human-derived tissues and biological products. This will decrease, or even eliminate, the need for further use of monkeys in the study of Creutzfeldt-Jakob disease and human prions.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences zoology mammalogy primatology
- natural sciences biological sciences biochemistry biomolecules proteins
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Coordinator
75651 PARIS
France
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