Prion diseases, including Creutzfeldt-Jakob disease, are currently untreatable and result in fatal neurodegeneration. Previous attempts to develop therapies for these conditions have had limited success, with benefits only being seen if treatment begins before or close to inoculation with the infectious agent. However, a recent study from Simon Hawke's group, published in Nature, shows that monoclonal antibodies can inhibit prion replication and delay the development of prion disease, even when given considerably later in the incubation period.

Prion-disease pathogenesis involves the transformation of normal cellular prion protein (PrPc) into an infectious disease-associated isoform, PrPSc. In this study, the authors generated prion-specific monoclonal antibodies (ICSM18 and ICSM35, which recognize PrPc and PrPSc with differing affinities) and tested whether these could block the transformation of PrPc to PrPSc in vivo.

Mice were inoculated intraperitoneally with a brain homogenate derived from terminally ill mice with scrapie and were treated twice weekly with ICSM18, ICSM35 or isotype-matched control antibodies. Even when given 30 days after prion infection (when the levels of PrPSc had reached a maximum in the inoculated mice), treatment with ICSM18 or ICSM35 resulted in considerably reduced levels of infectious protein in the spleens of treated mice compared with controls.

Does this treatment have positive effects on the health of the inoculated mice? Although the treatment was unsuccessful if given to mice after the onset of clinical disease, mice that were treated between 7 and 30 days after prion infection survived for up to 150% longer than isotype control-treated or untreated mice. Mice for which the treatment was continued remained healthy at the end of the study, showing no clinical signs of scrapie.

The authors conclude that although this treatment is not effective if given after clinical symptoms have developed and that there is a possibility that similar treatments could result in autoimmune side effects in patients, immunotherapeutic strategies for human prion diseases are worth pursuing.