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What's Inside Role of Iron in Neurodegeneration A Vaccine for Prion Disease? and Related Articles Industry News News from Other Countries Employment Opportunities |
A Vaccine for Prion Disease? A series of monoclonal antibody fragments that bind to the normal prion protein PrPC were tested in infected cell cultures expressing the abnormal prion protein PrPSC. Some, but not all fragments, were found to dramatically and dose-dependently reduce the levels of PrPSC without affecting the levels of PrPC. Duration of exposure to antibodies is critical. Cells passaged for seven days in the presence of antibody fragments had a high relapse rate and PrPSC levels returned to 50% of control (untreated culture) within seven days after removal of antibodies from the culture medium. By contrast, if cells were exposed to antibody fragments for two weeks, PrPSC levels remained undetectable even after four weeks of culture without antibody. To confirm that PrPSC had been cleared from the cultures, CD-1 Swiss mice were inoculated with antibody-treated and untreated infected cells. Mice inoculated with antibody-treated cells were free of prion disease 265 days later, whereas mice inoculated with untreated cells had a mean incubation time of 165 days. To explain their results, the authors propose that by binding to the normal protein PrPC on the cell surface, antibody fragments prevent the docking of PrPSC and the conversion of the PrPC to PrPSC. This blocks prion propagation. Over time (one to two weeks), residual PrPSC is eliminated through normal cellular degradation pathways. The results suggest that it may be possible to cure prion disease by developing drugs that bind critical regions on the PrPC protein. Recently, two approved drugs - the antimalarial quinacrine and the antipsychotic chlorpromazine- have been updated by the same group to block prion propagation in vitro (Proc. Natl. Acad. Sci. USA 2001; 98:9836). Clinical trials in patients are planned for both drugs, individually and in combination. Vaccines against prion disease may also be an alternative. The critical question remains whether the above in vitro results translate in vivo to patients. Source: Peretz A, Williamson RA, Kaneko K, et al. Antibodies inhibit prion propagation and clear cells of prion infectivity. Nature 2001; 412: 739-743. |
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