| First Author | Genoud N | Year | 2008 |
| Journal | Am J Pathol | Volume | 172 |
| Issue | 5 | Pages | 1287-96 |
| PubMed ID | 18372425 | Mgi Jnum | J:134268 |
| Mgi Id | MGI:3785209 | Doi | 10.2353/ajpath.2008.070836 |
| Citation | Genoud N, et al. (2008) Antiprion prophylaxis by gene transfer of a soluble prion antagonist. Am J Pathol 172(5):1287-96 |
| abstractText | 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 naive 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. |
