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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-4644

Genoud, N; Ott, D; Braun, N; Prinz, M; Schwarz, P; Suter, U; Trono, D; Aguzzi, A (2008). Antiprion prophylaxis by gene transfer of a soluble prion antagonist. American Journal of Pathology, 172(5):1287-1296.

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Abstract

Prion diseases are untreatable neurodegenerative disorders characterized by accumulation of PrP(Sc), an aggregated isoform of the normal prion protein PrP(C). Here, we delivered the soluble prion antagonist PrP-Fc(2) to the brains of mice by lentiviral gene transfer. Although naïve mice developed scrapie at 175 +/- 5 days postintracerebral prion inoculation (dpi), gene transfer before inoculation delayed disease onset by 72 +/- 4 days. At 170 days postintracerebral prion inoculation, PrP(Sc) accumulation and prion infectivity in PrPFc-treated brains were reduced by 3.6 and 4.2 logs, respectively. When PrP-Fc(2) was delivered 30 days after prion inoculation, survival of the treated animals was extended by 25 days. We then used tissue-specific recombination to express PrP-Fc(2) in the entire central nervous system, in only astrocytes, or in only oligodendrocytes. Oligodendrocyte-restricted PrP-Fc(2) expression impaired PrP(Sc) deposition and delayed disease even though oligodendrocytes are completely resistant to prion infection, suggesting that PrP-Fc(2) affords protection via noncell autonomous mechanisms. These results suggest that somatic gene transfer of prion antagonists may be effective for postexposure prophylaxis of prion diseases.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:04 Nov 2008 13:53
Last Modified:28 Nov 2013 00:27
Publisher:Elsevier
ISSN:0002-9440
Publisher DOI:10.2353/ajpath.2008.070836
PubMed ID:18372425
Citations:Web of Science®. Times Cited: 10
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Scopus®. Citation Count: 12

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