Illustrated by Maia Lazor

Holes in the Brain: The Fatal Implications of Prions

April Lin | SQ Summer 2024

Saltman QuarterlyStudent
··5 min read

Introduction

Kuru, or the laughing disease, was first discovered in the Fore people native to New Guinea. The Fore people upheld a tradition of funerary cannibalism, in which family members would eat the bodies of the recently deceased to help their spirit move on to the afterlife. Men often ate muscles, while women and children ate organs like the brain. Eventually, symptoms of kuru such as abnormal involuntary movements and tremors, along with pain and pathological laughter would emerge. Signs of kuru disease were more prevalent in women and children than in men. It was later determined that these individuals developed a disease called sporadic Creutzfeldt-Jacobs disease (CJD). This is caused by misfolded accumulations of proteins, or prions, that reside in the brain. As prions are highly contagious and largely transmitted through consumption, women and children who consumed infected brains eventually fell victim to the fatal diseases. Once the infected individual also passed and their family members engaged in funerary cannibalism of their body, more people within the tribe also contracted the disease of their relatives.

What are Prions?

A single prion in the brain is enough to cause fatal illness to the individual because prions can replicate. Prions, like all other proteins, lack DNA. However, they are unique in that just by interacting with normal proteins, prions can induce other proteins to misfold and become prions themselves. The method in which they cause normal proteins to mutate is not fully known and is still being studied. There are many kinds of illnesses that can result from exposure to prions, either through genetic inheritance (familial) or transmission (sporadic). These include CJD, fatal insomnia, Gerstmann-Straussler-Scheinker disease, scrapie, and Bovine spongiform encephalopathy (BSE), or mad cow disease, among others. All known diseases from prions are terminal. Treatment of the illness itself is difficult, as it can take years for symptoms to emerge but death can occur quickly after symptoms arise. CJD often causes death within months of onset. Furthermore, a certain diagnosis can usually only be made from a brain biopsy or autopsy, taken once the individual has already passed away. Autopsies may show actual holes in the brain due to cell death caused by the prions.

Creutzfeldt-Jacobs Disease

CJD is one such prion disease. There are four types of CJD, including sporadic CJD, which is the most common type. There is also variant CJD, familial CJD, and iatrogenic CJD, in which prion disease is spread from one individual with CJD to another non-CJD individual via medical treatment. The cause of sporadic CJD is not well known, much like the rest of prion mechanisms and diseases, though it is hypothesized to occur randomly when a normal protein misfolds into a larger aggregate prion. Variant CJD occurs through consumption of an animal infected with a prion disease, such as mad cow, which transfers from an infected animal to the human. In variant CJD, incubation before symptom onset can take around 10 or more years. Familial CJD is inherited when the prion protein gene, PRNP, from one parent is mutated and causes prion formation usually after the individual reaches adulthood. Familial causes of CJD, along with any other prion disease, are extremely rare. At its worst and final stage, all four types of CJD can cause dementia, loss of balance and mobility, and sporadic jerking movements, and are always terminal.

Fatal Insomnia

Fatal insomnia (FI) occurs through genetic inheritance of a mutated PRNP gene from at least one parent. The PRNP, or CD230, is a gene that encodes for prion proteins and is often associated with functions like neuroprotection, or protecting neurons from damage. However, mutation of the PRNP gene leads to harmful mutated proteins. It causes severe insomnia, which results in the death of the individual due to the brain damage that comes with severe sleep deprivation. Like in CJD, FI can either be familial (FFI) or sporadic (SFI). Both cases are extremely rare, but the disease occurs when prions damage the thalamus, “the sleep center” of the brain. The damage and cell death in this region of the brain leave the individual literally unable to fall asleep and also cause loss of motor coordination. Symptoms in sporadic cases are severe and can lead to death in as little as 7 months, and though individuals with SFI may not always report difficulties falling asleep, their sleep still shows abnormalities. On the other hand, familial cases are usually slower and eventually progress until the individual is completely unable to fall asleep, at which point they have reached the fatal stage of their illness.

Mad Cow and Scrapie

Bovine spongiform encephalopathy (BSE), or mad cow disease, is a prion disease that primarily affects cattle. Scrapie is another prion disease that affects sheep. Both diseases can be transmitted through BSE-contaminated feed, particularly meat-and-bone feed that was commonly provided to young animals in the 1970s. BSE and scrapie can cause mass outbreaks of CJD in the human population, since the currently-unknown infecting agent is often provided to thousands of herds. Leading up to 2004, Britain reported an epidemic of over 180,000 cases of BSE among 35,000 herds of cattle. In response, the British government has banned ruminant, or animal-based, feed for cattle and has implemented policies of removing high-risk parts like the brains from slaughtered animals.

Conclusion

Prions are an extremely complicated and dangerous disease to study, even though most of their mechanisms are still unknown. However, due to the danger that they pose and the lack of resources to diagnose and treat prion illnesses, more research is essential to tackle what could be considered one of the most horrifying diseases of the brain.

References