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.
View at publisher
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.
75 downloads since deposited on 04 Nov 2008
22 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||04 Nov 2008 13:53|
|Last Modified:||05 Apr 2016 12:31|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page