Recent developments in antibody therapeutics against prion disease

Preclinical evidence indicates that prion diseases can respond favorably to passive immunotherapy. However, certain antibodies to the cellular prion protein PrP^C can be toxic. Comprehensive studies of structure–function relationships have revealed that the flexible amino-terminal tail of PrP^C is instrumental for mediating prion toxicity. In a first-in-human study, an anti-prion antibody has been recently administered to patients diagnosed with sporadic Creutzfeldt–Jakob's disease, the most prevalent human prion disease. Moreover, large-scale serosurveys have mapped the prevalence of naturally occurring human anti-prion autoantibodies in health and disease. Here, we provide a perspective on the limitations and opportunities of therapeutic anti-prion antibodies.