Few pathogens inspire fear to the degree that prions do. As the culprit behind such mysterious diseases as mad cow disease and Familial Fatal Insomnia, prions are avoided at all costs. In December of 2003 more than 30 countries closed their borders to all beef imports from the United States because just one cow from the state of Washington tested positive for mad cow disease (1). But what are prions? And why do they evoke such aggressive responses?
Prions are not viruses but rather a misfolded form of a particular protein, called prion protein (PrP). This protein, whose function remains unclear, is found throughout the body of healthy individuals in its properly folded state, known as PrPC. When an individual is exposed to a prion, the misfolded form of PrP known as PrPSc, the prion can cause the normal protein to adopt its misfolded state. The normal PrPC is converted into the abnormal PrPSc, which can then go on to convert more healthy proteins into their pathogenic form. Eventually amyloid plaques of these abnormal proteins build up, mostly in neuronal tissue, causing transmissible spongiform encephalopathies, holes in the brain that continue to grow until the individual has passed away.
Prion diseases are universally fatal and there is no currently approved treatment to slow their advance (P). Because these diseases occur due to a single misfolded protein, they are not reliant on a nucleic acid based entity for transmission, as is every other known transmissible disease. It is for this reason that prions are not susceptible to normal sterilization procedures, including high temperatures and UV radiation. Transmission can occur solely due to ingestion of infected neural tissue or, as more recently suggested, via inhalation of air droplets (2). Because there is no known treatment for prion diseases countries tend to go to relatively extreme measures to prevent prions from crossing their borders.
However, new research suggests that the use of PrP antibodies, both prophylactically and after infection has taken root, might help slow prion disease progression (3, 4, 5, 6). These antibodies bind to specific regions of the normal PrP protein, helping them resist conversion to their prion form (4). However, these have mostly involved in vitro studies, which do not necessarily mean that there are practical clinical uses for anti-PrP antibodies in treating prion diseases. One of the main hurdles to overcome is getting these antibodies to target tissues in the central nervous system at concentrations high enough to have an effect. In order to do this the blood brain barrier (BBB), which is normally impermeable to antibodies, must be overcome. In the past this has meant inserting the drugs directly into the brain of mouse models. However, it would be more suitable in human patients for a less invasive delivery method to be used, especially considering the possible transmission of prions that could occur during brain surgery.