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British Medical Bulletin 66:281-292 (2003)
© 2003 Oxford University Press

Approaches to prophylaxis and therapy

An investigation into prion disease diversity

Dominique Dormont

Service de Neurovirologie, CEA, CRSSA, EPHE, Univeristé Paris XI, Fontenay-aux-Roses, France

Despite important progress in experimental treatment of neurodegenerative diseases, no therapeutic strategy has today proven its capability to cure or even to stabilise human TSEs. Pathogenesis experiments performed in rodent TSE models have shown that central nervous system damages are detectable long before the appearance of the clinical symptoms. At the time of disease onset, PrPSc accumulation has almost reached its highest level, and the neuropathological lesions (spongiosis, gliosis) are as intense as they are at the time of death. Therefore, the neurodegeneration that is present at the onset of the disease is beyond therapy, and, in theory, only a preclinical diagnosis of TSEs would permit the prevention (or delay) of neurodegeneration. Unfortunately, there are no diagnostic tests that can be used to show TSE agent infection during the preclinical phase of the disease. Nevertheless, since the appearance of variant Creutzfeldt-Jakob disease (vCJD), those in the scientific community working on experimental therapy have increased their efforts. Tens of drugs have been tested in several experimental models, and there are some high-output screening platforms being used in Europe and in the US. Any rational therapeutic strategy needs to be based on pathogenesis data and/or knowledge on the nature of the causative agent. Therefore, progress in therapy is tightly linked to a better understanding of the basic science of TSE.


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