Minds on Medicine: The Unsolved Problem of Prions
What are prion diseases?
Prions are small infectious protein particles which induce the “prion protein”, normally found within nerves in the central nervous system, to fold abnormally. These abnormally folded prion proteins aggregate and form long, insoluble clumps known as fibrils, which can trigger the death of neurons in the nervous system. This results in different types of neurodegenerative diseases with extensive neuronal loss; prion diseases are rare, but ultimately fatal. Mad Cow Disease is a well known example of a prion disease, which is scientifically called Bovine Spongiform Encephalopathy (BSE).
How are prion diseases transmitted?
Similar to other bacteria and viruses, prions can be transmitted via ingestion, blood transfusion or through medical equipment. It is unknown how prions are transmitted from one neuron to another - some theories include the idea that neurons expel the prion into their surrounding extracellular space, and the prions are then taken in by other adjacent neurons; or that there may be tunnelling nanotubes between neurons via which prions are transmitted. Kuru is a prion disease which was spread in Papua New Guinea during the 1950s and 1960s due to people eating the infected brains of dead ancestors as part of a funeral rite. Kuru symptoms include slurred speech, tremors, abnormal gait and mood changes and death usually occurs within a year of infection. Such cannabalism is now a lot less common, meaning the disease has almost disappeared.
However, unlike bacteria and viruses, prions can be inherited. Inherited prion diseases are associated with mutations in the prion protein gene - for example in the case of fatal familial insomnia (FFI). Furthermore, prion diseases can even originate sporadically. Creutizfeldt-Jakob disease (CJD) is an example of a human prion disease which most commonly occurs sporadically. Symptoms of CJD include slurred speech, problems with vision, blindness, abnormal jerky movements, loss of intellect and progressive loss of brain function and mobility. Death due to CJD usually occurs within a year. It is thought that the prions which cause CJD are of a very similar strain to those which cause BSE - and may even be identical. In studies on mice, it has been found that mice infected with CJD prions have almost “identical” symptoms and incubation periods as mice infected with BSE prions, and microscope analysis revealed a similar extent of neuronal damage in the central nervous system in both cases (findings by Scott et al, 1999). However, unlike CJD, BSE is transmitted by consumption of meat from cows also infected with the BSE prion.
Why are prion diseases so hard to treat?
Unlike bacteria and viruses, prion diseases are irreversible and can not be overcome by the body’s immune system. As of yet, there are no medical drugs or other types of advances for the treatment of prion diseases. It is likely that there is a lack of research into prion diseases compared to other infectious disease due to the relative rareness of prion diseases.
Crucially, prions are exclusively formed of proteins and contain no nucleic acid genetic element. Experimentally, if viruses, bacteria and prions were exposed to ultraviolet irradiation, which inactivates and destroys nucleic acids, prion infections are the only infections which can persist. Furthermore, despite being exclusively protein particles, prions are protease resistant (proteases are enzymes which degrade proteins). This makes prevention of prions diseases difficult - for example if medical equipment is infected with prions, radiation and heat therapy are unlikely to destroy the prion and further use of the equipment could lead to iatrogenic prion transmission.
Prion diseases are caused by the misfolding of prion protein, and these diseases are continuous due to the continuous production of prion protein in neurons in the brain. Thus, theoretically, gene therapy which inhibits the expression of prion proteins in neurons could be a potential prion disease treatment option. However, this hypothesis is currently a far reach as it is not yet known what other important roles prion proteins may play in the brain - hence inhibition of the protein through gene therapy could cause significant unwanted side effects. An alternative potential therapy could be encouraging the clearance of aggregations of misfolded prion protein, perhaps through antibodies specific to such aggregations.
Conclusion
In conclusion, prion diseases are an area of neurodegenerative diseases which relatively little is known about. This is most probably due to how rare prion diseases occur. However, previous prion diseases offer interesting insight into how these diseases are transmitted and cause disease, and also insight into potential future treatment avenues.