Transmissible spongiform encephalopathies (TSEs), also known as
prion diseases, describe a group of fatal
neurodegenerative disorders affecting both humans and animals. Accumulation of misfolded
prion proteins is the pathological hallmark of these disorders; such accumulation occurs in lymphoreticular tissue prior to CNS involvement in
scrapie, experimental models and human
variant Creutzfeldt-Jakob disease. Lymphoreticular accumulation of misfolded
prion protein has not been demonstrated in human sporadic or genetic forms of TSE. Once clinical symptoms develop, all
prion disorders have a rapidly progressive and lethal course, and no effective
therapy exists. In the past 10 years, antibody-based
immunotherapy has been considered for other
neurodegenerative disorders associated with
protein misfolding and, therefore, might also be an effective approach to prevention or treatment of
prion disease. Self-tolerance to endogenous
prion protein is, however, a major challenge to the development of effective
immunotherapy, as is the risk of adverse effects from active immunization. This Review summarizes the evidence that immunization could slow
disease progression or increase lifespan in animal models of
prion diseases. The therapeutic potential of these strategies in treating patients with
prion diseases is also discussed.