The lack of an immune response to prions--the infectious proteins that cause scrapie, bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD)--might be related to the fact that these agents do not contain nucleic acids (genetic material).
Hans Kretzschmar from Ludwig-Maximilians University and colleagues from the Technical University Munich, Germany, and Coley Pharmaceuticals, aimed to use genetic material (a specific type of nucleotide arrangement called CpG oligodeoxynucleotides) as a form of disease treatment after prion infection in mice. CpG oligodeoxynucleotides have previously been shown to stimulate the immune response.
The investigators inoculated 24 healthy mice with brain extracts from mice infected with scrapie prions, and then injected CpG oligodeoxynucleotides. This procedure resulted in 38% longer survival times than a control group that were injected with saline solution; longer survival times occurred when CpG oligodeoxynucleotides were given repeatedly over a three-week period.
Hans Kretzschmar comments: "The most likely explanation is the stimulation of TLR9-expressing cells of the innate immune system such as macrophages, monocytes, and dendritic cells. CpG oligodeoxynucleotides have not been shown to have adverse effects to human health and could therefore be considered as a therapeutic choice after prion infection."
In an accompanying Commentary (p 184), George Carlson from the McLaughlin Research Institute, USA, states that the approach of Kretzschmar and colleagues is reasonable, and concludes: "Development of improved diagnostics and postexposure prophylaxis are urgently needed given the unknown prevalence of subclinical prion infection associated with the BSE outbreak."
Contact: Professor Hans A Kretzschmar, Institut fur Neuropathologie, Ludwig-Maximilians-Universitat, Marchionistrasse 17, 81377 Muenchen, Germany; T) +49-89-7095-4900; F) +49-89-7095-4903; E) hans.kretzschmar@inp.med.uni-muenchen.de
Dr George A Carlson, McLaughlin Research Institute, 1520 23rd Street South, Great Falls, Montana 59405, USA; T) +1 406 454 6044; F) +1 406 454 6019; E) gac@mri8.mri.montana.edu
The Lancet