Prions are unique infectious agents, unlike typical bacteria or viruses, that cause fatal neurodegenerative diseases. They are misfolded proteins capable of inducing normal proteins to also misfold. This unusual nature presents significant challenges in understanding and preventing the diseases they cause.
Understanding Prions
Prions are fundamentally misfolded versions of a normal protein, known as cellular prion protein (PrPC), which is found on the surface of cells, particularly in the central nervous system. When PrPC undergoes a conformational change, it transforms into an abnormal, disease-causing form called scrapie prion protein (PrPSc). This PrPSc acts as a template, prompting healthy PrPC proteins to refold into the infectious, misfolded shape.
This conversion process leads to the accumulation of PrPSc in the brain, forming aggregates resistant to degradation by cellular enzymes called proteases. The progressive buildup of these abnormal proteins within neurons damages them, causing the brain tissue to develop a characteristic sponge-like appearance with holes. Prions are not living organisms, as they lack genetic material like DNA or RNA.
Acquired Transmission Pathways
Prions can be transmitted from external sources. A primary pathway is ingestion of contaminated tissues. Examples include Bovine Spongiform Encephalopathy (BSE), or “mad cow disease,” which spread in cattle through contaminated feed and was linked to variant Creutzfeldt-Jakob disease (vCJD) in humans who consumed infected beef products.
Kuru, a human prion disease, was transmitted through ritualistic cannibalism in Papua New Guinea through consumption of infected human brain tissue. Chronic Wasting Disease (CWD) in deer and elk also spreads through direct contact or environmental contamination. Prions resist conventional cooking and digestion, making them difficult to eliminate from contaminated food.
Iatrogenic transmission, through medical procedures, is another route. This involves inadvertent transfer via contaminated surgical instruments, especially neurosurgical tools used on high-infectivity tissues like the brain and spinal cord. Historically, cases have also been linked to corneal transplants, dura mater grafts (tissue used to repair the brain’s outer covering), and growth hormone derived from human pituitary glands. Prions resist standard sterilization procedures like boiling or typical autoclaving, posing a challenge for decontamination.
A “species barrier” influences prion transmission between different species. This barrier refers to inefficient transmission between species, often due to differences in their normal prion protein’s amino acid sequences. While some prions, like those causing scrapie in sheep, are not known to transmit to humans, others, such as BSE prions, have successfully crossed this barrier to infect humans, albeit rarely. Overcoming this barrier can lead to prolonged incubation periods or inefficient disease development in the new host.
Hereditary Prion Diseases
Some prion diseases arise from inherited genetic factors rather than external exposure. These hereditary forms, including Familial Creutzfeldt-Jakob Disease (CJD), Fatal Familial Insomnia (FFI), and Gerstmann-Sträussler-Scheinker syndrome (GSS), are linked to specific mutations in the PRNP gene. This gene provides instructions for making the normal prion protein (PrP). Over 60 different mutations have been identified in the PRNP gene, with five common mutations accounting for approximately 85% of genetic prion disease cases.
These inherited mutations make the normal PrP protein more susceptible to spontaneously misfolding into the abnormal PrPSc form. This spontaneous misfolding, rather than an external infectious source, initiates the disease process. The accumulation of these misfolded proteins then leads to neurodegeneration over time. The outcome is similar to acquired forms, but the “transmission” is a genetic predisposition passed down through generations.
Preventing Prion Spread
Preventing prion transmission involves a multi-faceted approach, focusing on controlling exposure routes. In food safety, stringent measures have been implemented, such as bans on feeding ruminant-derived proteins to other ruminants to prevent the spread of diseases like BSE. Livestock testing programs and the removal of specified risk materials (SRMs), which include brain and spinal cord tissues where prions accumulate, from the food chain are also employed. These regulations aim to minimize the risk of contaminated meat entering the human food supply.
Medical and surgical protocols have been adapted to address the unique resistance of prions to conventional sterilization. This includes strict guidelines for reprocessing surgical instruments, particularly those used in neurosurgery on brain and spinal tissue. The use of single-use instruments where feasible and enhanced sterilization methods, such as prolonged exposure to high temperatures (e.g., 134°C for at least 18 minutes in a porous load autoclave) or strong chemical treatments (e.g., 1N sodium hydroxide or 20,000 ppm sodium hypochlorite solution for one hour), are recommended. Additionally, screening of blood and tissue donors helps reduce potential iatrogenic transmission.
In research and laboratory settings, rigorous safety protocols are in place for handling and disposing of prion-infected materials. This includes specific containment levels, often Biosafety Level 3 for unfixed brain or spinal cord samples, and comprehensive training for personnel on the nature of prions and appropriate handling procedures. Contaminated surfaces and disposable materials are typically treated with strong chemical solutions or incinerated to ensure complete inactivation of prions.