Prion Diseases

Prions refer to abnormal pathogens that are transmissible and cause problems in the brain. Transmissible spongiform encephalopathies are a group of diseases associated with the protease-resistant protein (PrP). The exact function of PrP is unknown, although it is thought to be involved in the transport of copper into cells, neuroprotection and neuronal communication.^[1] The PRNP gene that codes for PrP is located on chromosome 20p13 and it is estimated that 10-15% of prion diseases are linked to changes in this gene ^[1].

Sporadic or acquired prion diseases are thought to account for the remaining 80-90% of prion diseases ^[1]. Sporadic types include sporadic Creutzfeldt-Jakob disease (sCJD) and sporadic fatal insomnia (sFI), while acquired types include those resulting from exposure to outside sources including variant Creutzfeldt-Jakob Disease (vCJD) which is obtained from consuming infected beef and kuru, obtained from eating infected human remains ^[1]. Regardless of the route of exposure, all prion disease have the potential to be infectious. This article will provide detailed information on prior diseases, including the different types and the symptoms that manifest. Management information will be provided, with the caveat that this is a relatively unknown area in medicine.

Abnormal Structure

The infectious prion protein differs from the healthy prion protein in their folding structure which results in decreased solubility and increased resistance to protease or normal protein breakdown ^[2]. There are two theories as to how the abnormal prion proteins can then spread and cause disease. The first is the seeding theory which proposes that the prion protein exists in multiple forms, the misfolded prion protein is less stable than the regular prion protein and will quickly refolds back to the common form of prion protein ^[3]. In the seeding theory, the misfolded protein only creates disease if it binds with another misfolded protein to create a more stable dimer that can further bind with additional misfolded types ^[3].

The second theory is the refolding model which proposes the introduction of a misfolded protein that can bind to normal folded prions and transform them to the misfolded type ^[3]. Regardless of the formation, it is generally accepted that misfolded prions bind to form more stable structures and the body cannot break down these misfolded proteins at the rate that they are formed ^[4]. The bound prion proteins create increased levels of oxidative stress and it is thought that when paired with the loss of normal protein function, triggers neurodegeneration in an attempt to contain the pathological prions ^[4].

Types and Symptoms

Prion diseases are expressed in a number of different diseases that affect different areas of the brain. Creutzfeldt-Jakob Disease (CJD) is the most prevalent spongiform in humans ^[5]. CJD presents as dementia, jerky muscle contractions and the loss of controlled body movements ^[5]. Death occurs 6 months to 2 years after symptoms begin presenting however the incubation period is thought to be significantly longer. CJD can be both variant and classic types, these two differ in their presentations. Variant CJD typically affects younger individuals and has a longer duration of illness with primary symptoms being psychiatric or behavioural symptoms, while Classic CJD presents in older individuals, affects the cerebral cortex and presents primarily with dementia and early neurological signs ^[5]. Iatrogenic Creutzfeldt-Jakob Disease (iCJD) is the prion disease resulting from medical treatments. First discovered after 200 individuals developed iCJD after receiving contaminated human cadaveric pituitary-derived growth hormone, iCJD is also thought to have been transmitted through dura mater transplants and corneal transplants ^[1]. There have been some reports of additional cases of iCJD that were thought to have been transmitted by blood transfusions.

Other prion diseases include Fatal Familial Insomnia, Kuru and Gerstmann-Straussler-Scheinker disease. Fatal Familial Insomnia affects the thalamus, causing difficulty falling asleep and loss of control of bodily movements eventually progressing to the inability to fall asleep ^[6,7]. Kuru is associated with the Fore Natives of Papua New Guinea highlands where cannibalism was part of their burial rituals. Kuru presented primarily in females and children who were more likely to eat the brain or part of the nervous tissues ^[6,8]. Kuru, which means ‘shake’, primarily affects the cerebellum and presents with signs of loss of coordination, difficulty walking and shaking that resembled shivering ^[8]. Gerstmann-Straussler-Scheinker presents with a loss of coordination and clumsiness but there is typically less jerking than other prion diseases ^[9]. Symptoms of Gerstmann-Straussler-Scheinker typically begin earlier than CJD and progress much slower.

Animals can also be impacted by prion diseases including Scrapie Disease and Bovine Spongiform Encephalopathy (BSE), commonly referred to as Mad Cow Disease ^[6]. The result is an increased risk for humans, depending on food consumption as discussed below. Transmissible spongiform encephalopathies typically present in the brain stem of animals. Scrapie affects sheep and goats, with clinical symptoms only presenting in adult animals. Scrapie is thought to occur as a genetic susceptibility rather than from exposure to contaminated food. BSE presents in cattle and is thought to have originated from contaminated meat-and-bone meal containing BSE-infected products from spontaneous BSE or from feeding cows infected sheep products, peaking in Great Britain in 1992 ^[6]. Additional animal spongiform encephalopathies include Chronic Wasting Disease in mule, deer and elk, and additional infections associated with BSE-contaminated foodstuffs including Feline Spongiform Encephalopathy and Transmissible Mink Encephalopathy ^[6].

Overall, if you develop symptoms that are otherwise unexplained and include memory impairment, behavioural changes, or any changes with controlling your movements, it would be worth evaluating your risks to prion diseases. Note that many of these changes mimic dementia and cognitive decline. They could potentially develop over long periods of time, but there is not a complete understand of these conditions as of yet.

Risk Factors

Risk factors for transmissible spongiform encephalopathies include genetics, consuming contaminated food products and receiving infected human products. There are certain genetic changes in the prion protein that are thought to put some at higher risk of prion disease than others. One of these includes a methionine/methionine genotype at codon 129 of the prion protein which is associated with higher risk of getting variant CJD. Since iCJD was discovered, the American Red Cross has restricted donations from individuals who spent 3 or more months in the United Kingdom between January 1980 to December 1996, which was around the peak incidence of BSE. The American Red Cross further restrict individuals who have ever received dura mater transplants or human pituitary derived growth hormone.

Prevention and Treatment

For infected animals, there is a strict ‘stamping out’ policy for animals infected with prion disease that involves the humane destruction of all infected animals, tracking of potentially infected or high risk animals, quarantine and animal movement controls. Zoning of infected verses disease-free areas are used to limit the potential for spread of prion disease in animals. For humans, the best way to prevent spread during medical procedures is to destroy any potentially contaminated surgical instruments as current sterilization procedures do not destroy prion proteins.

The bad news is that there is no specific conventional treatment for prior diseases. Largely, symptoms are managed as best as possible. From a naturopathic perspective, diet and lifestyle can be optimized to ensure overall health is maintained. A Naturopathic Doctor can make recommendations in terms of optimal nutrition, ensuring adequate vitamins, minerals, and nutrients are consumed. This would prevent nutrient deficiencies. Furthermore, treatments could be tailored to improve optimal brain function, as one might do for dementia. Utilizing acupuncture for symptom management is a promising option, since acupuncture can be quite effective for nerve and muscle problems. Herbs like Bacopa or Ginkgo could be used on a trial basis to see if any of the cognitive symptoms improve. Finally, it’s always important to know where your meat comes from. It is recommended that humans consume organic meats with a verified source. Prion diseases are a difficult and mysterious set of conditions. If you have any questions, please see your Naturopathic Doctor.