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Science 31 October 2003:
Vol. 302. no. 5646, pp. 871 - 874
DOI: 10.1126/science.1090187
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Reports

Depleting Neuronal PrP in Prion Infection Prevents Disease and Reverses Spongiosis

Giovanna Mallucci, Andrew Dickinson, Jacqueline Linehan, Peter-Christian Klöhn, Sebastian Brandner, John Collinge*

The mechanisms involved in prion neurotoxicity are unclear, and therapies preventing accumulation of PrPSc, the disease-associated form of prion protein (PrP), do not significantly prolong survival in mice with central nervous system prion infection. We found that depleting endogenous neuronal PrPc in mice with established neuroinvasive prion infection reversed early spongiform change and prevented neuronal loss and progression to clinical disease. This occurred despite the accumulation of extraneuronal PrPSc to levels seen in terminally ill wild-type animals. Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity.

Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1, UK.

* To whom correspondence should be addressed. E-mail: j.collinge{at}prion.ucl.ac.uk

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