Finding a method to target the abnormal proteins that cause prion diseases, such as scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt–Jakob disease (CJD), could lead to new treatments or prevention strategies for these fatal diseases. A recent study suggests that harnessing RNA interference (RNAi) technology could be a promising approach.

Previous work has shown that genetic deletion of the normal form of PrPC, the protein that becomes malformed to cause scrapie, can protect against disease development. Now, Alexander Pfeifer of the University of Bonn, Germany, and colleagues have shown that knocking out the protein in only a proportion of brain cells is effective, leading Pfeifer to suggest that this might be “a promising therapeutic option” (BBC News, 4 December 2006).

Despite these encouraging findings, the researchers urged caution. Pfeifer says: “It will take years before the method can be used on human beings” (University of Bonn, 4 December 2006). Approximately two-thirds of brain cells need to carry the transgene responsible for knocking out PrPC to prevent disease progression. Targeting this number of brain cells in adult humans could be difficult, and improving current methods of gene delivery will be necessary. As Adriano Aguzzi from the University Hospital of Zurich, Switzerland, puts it, the researchers face “an engineering problem” (News @ nature.com, 1 December 2006).

Other researchers have highlighted the potential adverse effects of RNAi, including off-target effects and unknown consequences of deleting normal PrPC. Qingzhong Kong from the Case Western Reserve University, USA, says that: “Much more research is needed” (BBC News, 4 December 2006) and argues that other therapeutic interventions, such as a vaccine against prion proteins, would be easier to administer.