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Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance

Abstract : Prion diseases are fatal and transmissible neurodegenerative disorders. Infectious forms include iatrogenic Creutzfeldt-Jakob disease after human cadaver-sourced growth hormone treatment (hGH-iCJD). Our understanding of the factors governing the pathophysiology of infection, upon exposure to an exogenous prion, remains very limited in humans. The aim of this study was to better understand these phenomena using data from the French cohort of patients who were exposed to this at risk treatment. Using Cox hazards model, we provided the first epidemiological evidence of a relationship between dose of exposure and disease occurrence on one hand and incubation time on the other hand. Incubation period modelling by Weibull distribution estimated that 95% of the cases have already occurred. In a descriptive study, we showed that clinical and neuropathological features resembled other forms of infectious prion diseases after a peripheral contamination supporting a major role of the route of exposure. We also performed experimental transmission to transgenic mice expressing human PrP to test our hypotheses about the infecting prion strain that were transmitted to French hGH-iCJD patients. To conclude, we identified factors implicated in human prion transmission and provided a methodological frame and useful information that could help to evaluate the transmission risk associated with other brain proteinopathies such as Alzheimer and Parkinson’s diseases for which a prion-like mechanism has been proposed.
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Submitted on : Monday, November 12, 2018 - 11:14:06 AM
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  • HAL Id : tel-01919102, version 1

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Laurène Peckeu. Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance. Physiologie [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066583⟩. ⟨tel-01919102⟩

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