Prion diseases - A tale of cows and cannibals

Proteins play a part in most of our bodily functions, making up our antibodies and enzymes along with serving various structural and regulatory roles. Proteins are large molecules, consisting of chains of amino acids known as polypeptides. These polypeptides can fold into a three-dimensional structure, determined by the bonds and interactions between its amino acids.

However, proteins do not always fold correctly into fully functional shapes. It is believed that some misfolded proteins can bind to other proteins of the same type, inducing their normal neighbours to contort into their distorted state.¹ This triggers a chain reaction, causing more and more proteins to become “infected”, similar to the spread of pathogens such as bacteria or viruses.¹ These abnormal proteins then clump together, forming aggregates called amyloids.² When these aggregates accumulate on the axons of neurons, they lead to axon dysfunction and neuronal death³, ultimately manifesting as a set of diseases collectively known as transmissible spongiform encephalopathies (TSEs).

Prions are very stable—since they do not contain nucleic acids, they cannot be destroyed by ultraviolet radiation, unlike most other infectious agents.¹ A study by the National Institute of Allergy and Infectious Diseases found that a tissue sample from a prion disease patient managed to infect four out of eight mice even after being preserved in formaldehyde, embedded in wax, and kept on dry specimen slides for three years⁴. Worst of all, while some prion diseases have been linked to genetic and familial factors, some are believed to strike sporadically—suddenly and without warning.

There are many types of prion diseases, and not all of them affect humans. However, all prion diseases have one thing in common—their effects are devastating.

In the 1990s, cattle in the United Kingdom began to show symptoms of a neurological disease which worsened over time, resulting in behavioural changes, trembling and eventual death. This was dubbed the “mad cow disease” after its bovine origins. A prion disease known as variant Creutzfeldt-Jakob disease (vCJD) began to manifest in a very small percentage of people following this. It is believed that this disease was tied to the consumption of nerve tissue from the infected cows.⁷ The timeline of these cases lent credence to one of the hypotheses surrounding prion diseases at the time—that it could take years after the initial infection for symptoms to materialise due to the long incubation periods of prion diseases.⁸

Perhaps the prion disease with the most nightmarish symptoms of all is Fatal Familial Insomnia. As its name suggests, those suffering from Fatal Familial Insomnia gradually lose the ability to fall asleep, eventually ending up in a state described as a “waking coma” before succumbing to the disease.⁹ This happens because prions damage the thalamus (the part of the brain that regulates sleep) until the patient is completely unable to sleep, resulting in a host of health complications such as excessive sweating, rapid heart rate and problems with memory and attention.⁹ These symptoms progressively worsen over months, lasting an average of 18 months between the onset of insomnia and eventual death.⁹ Though this disease largely affects those with a family history of fatal insomnia, sporadic cases with no genetic history of the disease have also been detected⁹.

Despite how disturbing some of this may sound, strides are being made in the treatment and study of prion diseases. At University College London, researchers recently uncovered a type of protein occurring naturally in the brain with the ability to “really throw a spanner into the works in terms of prion propagation,” according to neurologist and molecular biologist John Collinge.⁶ And in 2021, a team of researchers at Imperial College London and the University of Zurich were able to study the molecular mechanism behind the misfolding of prions and produce antibodies to successfully stop prions from transitioning into their infectious form.¹⁰

So at the end of the day, are prion diseases something worth losing sleep over? (Sorry.) On the bright side, prion diseases are incredibly rare—only around 300 cases are reported in the United States each year.¹¹ On a less cheerful note, the annual mortality rate of sporadic Creutzfeldt-Jakob disease (sCJD) seems to have increased in the past twenty years, especially in countries with ageing populations such as Japan.¹² According to Dr Yoshito Nishimura, a researcher from Okayama University, "CJD, albeit rare, will be more prevalent in the next 5-10 years." ¹²