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Monoclonal antibodies inhibit prion replication and delay the development of prion disease


Prion diseases such as Creutzfeldt–Jakob disease (CJD) are fatal, neuro-degenerative disorders with no known therapy. A proportion of the UK population has been exposed to a bovine spongiform encephalopathy-like prion strain1,2,3 and are at risk of developing variant CJD4. A hallmark of prion disease is the transformation of normal cellular prion protein (PrPC) into an infectious disease-associated isoform5, PrPSc. Recent in vitro studies indicate that anti-PrP monoclonal antibodies with little or no affinity for PrPSc can prevent the incorporation of PrPC into propagating prions6,7. We therefore investigated in a murine scrapie model whether anti-PrP monoclonal antibodies show similar inhibitory effects on prion replication in vivo. We found that peripheral PrPSc levels and prion infectivity were markedly reduced, even when the antibodies were first administered at the point of near maximal accumulation of PrPSc in the spleen. Furthermore, animals in which the treatment was continued remained healthy for over 300 days after equivalent untreated animals had succumbed to the disease. These findings indicate that immunotherapeutic strategies for human prion diseases are worth pursuing.

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Figure 1: Anti-PrP antibodies inhibit splenic PrPSc protein levels.
Figure 2: Immunohistochemistry of spleens from antibody-treated mice.
Figure 3: PrPSc protein levels in mice with extended survival.


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This work is supported by grants from the Medical Research Council (UK). We thank D. Walsh and S. Gentleman for help with the immunohistochemistry.

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Correspondence to Simon Hawke.

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S.H., J.C. and D.A. are consultants to and founder shareholders in D-Gen Ltd.

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White, A., Enever, P., Tayebi, M. et al. Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature 422, 80–83 (2003).

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