Bovine spongiform encephalopathy

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By Kevin Pan


Transmissible spongiform encephalopathies are known as prion diseases that are progressive neurological disorders. This group of diseases includes Kuru, which is a disease found among New Guinea natives, Gerstmann-Straussler-Scheinker disease and bovine spongiform encephalopathy. Bovine spongiform encephalopathy is a progressive neurological disorder in cows that arose in the 1980’s.. BSE has an incubation period of about four years and affects adult cattle at the peak onset of 4-5 years. Humans can be infected with this disease after eating products that have been tainted with this disease. While the exact method of transfer is still not understood, the disease is not believed to be a product of bacteria, viruses, parasites and fungus (eden.lsu). It is believed that a misfolded protein known as the prion protein in cattle is the cause of transfer. Prion proteins are commonly found throughout the body, but they can be modified if there is an accumulation of the modified prion proteins (edeu.lsu). Eventually, a high accumulation of these protein can lead to damaged and disease. A major issue with this protein is that it is difficult to kill as it is able to survive heat, UV light, ionizing radiation and normal sterilization techniques1. The prion is also partially resistant to Proteinase K, a type of amino acid breakdown. This leads scientists to believe that the prion is not destroyed in the gastrointestinal tract (Campbell 2006). It is believed that the variant Creutzfeldt-Jakob disease, which is the human form of BSE, is caused by BSE. However, studies have shown a similarity between prions of BSE and TSE, but not a directly correlation to support that theory2. Symptoms of CJD are dementia, memory loss, personality changes and hallucinations. Mad Cow Disease was first found in cattle in England in 1986 and thousands of cattle died due to the disease. [[Image:BSE_001sm.jpg|thumb|300px|right|Figure 1). Brain infected by prion disease. Heavy restrictions were placed on cattle export throughout the world, with heavy restrictions occurring in Europe. The USDA implemented stringent measurzes, banning products from nations where BSE was found. Between 1985-95, it is believed that almost 1 million cattle have been infected in the UKK and about ¾ of those were fed to humans (Campbell 2006). This ban on UK beef was removed in May 2006. Recent studies have shown a link between bovine prion disease and Alzheimer’s disease.

By Kevin Pan

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Prion Diseases

A prion is a type of protein that triggers normal proteins in the brain to fold abnormally, which affect the nervous system in humans and animals and can cause numerous afflictions (Prion Diseases Johns Hopkins). One of the earliest known prion diseases is called “scrapie,” which has been around since 1732. This degenerative disease affects the nervous systems of sheep and goats and can e characterized by animals scraping off their fur or wool. Other symptoms of the disease are changes in behavior, tremors and locked muscles and experiencing a loss of movement. Scrapie affects sheep between the ages of three to five years old and once infected, the animals generally die within 2 weeks to 6 months of onset. Dissections of afflicted sheep show the proteins’ presence in the nervous system, tonsils, muscles and many other organs. Healthy mammals have normal prion proteins (PrPC), which have amino acid sequences that are highly conserved in mammalian species. This protein consists of 254 amino acids, which includes a signal peptide at the N-terminus, as well as the c-terminus. The protein also includes two asparagines for nitrogen glycosylation (Hagiwara 2013). Unlike other infectious agents, prions are unique in that they do not have nucleic acids (Korth et al 2001). Comparing the two proteins with each other can elicit several differences. Firstly, it was shown through infrared spectroscopy that the normal prion protein consists of roughly 40% α-helixes, whereas PrPSc was shown to have a higher β-sheet (54%) content than α-helices (21%) content. It is believed that this high β-sheet content is what makes the misfolded proteins pathogenic (Hagiwara 2012). It was found that human prion diseases are closely related with two types of scrapie prion proteins that can be detected using a Western blot based on the size of PrPSc (Gambetti et al 2003).

The symptoms that are associated with scrapie are also commonly associated with other prion diseases. Common symptoms of these other diseases include impaired brain function, memory changes, personality changes and behavioral changes. These conditions commonly arise in adulthood and cause a very rapid deterioration (Genetics Home reference). These disorders are very rare affecting about one person per million worldwide—only 350 new cases are reported annually in the United States.

The most common type of Prion Diseases are Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). 10-15% of these disorders are caused by mutations to the PRNP gene on chromosome 20, which encode the prion protein (PrPC). This prion protein is found in its highest concentrations in the central and peripheral nervous systems. The other 85-90% of cases are classified as sporadic or acquired. People who have sporadic prion disease have no family history of the disease (Prion Disease 2014). The actual function of this protein is unknown, but researchers believe that this protein can transport copper into cells, protect the brain cells from injury and communicate between neurons (Prion Disease 2014)10. Mutations to this gene form produce an abnormally shaped protein called PrPSc, which binds to PrPc. This binding to normal protein forms protein-protein interactions and recruits more PrPC into the mutated form. A build-up of this abnormal protein leads to clumping in the brain, which forms sponge-like holes in the brain (Prion Disease 2014).

Analysis of people affected with variant Creutzfeldt-Jackob disease has shown that affected individuals were homozygous for methionine at PRNP codon 129. In a study conducted by Asante et al 2002, they were able to show that mice homozygous for methionine at 129 acquired the prion disease after inoculation with BSE. Amongst the Caucasian population, roughly 50% of the individuals are homozygous for M, about 35% are heterozygous for MV and the rest are homozygous for valine.

Prion diseases that are acquired are due to exposure to PrPSc. An example of an acquired disease is Variant Creutzfeldt-Jakob disease, which can be obtained from eating cows that have been afflicted with BSE.


Transmission of prions between similar mammalian species is efficient, whereas transmission between different species is affected by the “species-barrier”(Hagiwara et al 2013). That is it is more difficult to transfer the disease to humans, so there are longer incubation periods for the disease. It is believed that the main source of this disease in cattle originated from the food served to the cattle. Cows are naturally herbivores, so they do not rely heavily on eating meats. However, many cattle were served a protein supplement, which was a combination of meat and bone meal. This combination came from leftover food and carcasses of other animals.


There has been a decline in cases of mad cow disease recently due to a ban on feeding cattle meat and bone meat. Besides feeding surveillance, important regulations are important for containing this disease. In England, a stringent control system was implemented that prevented any animals over 30 months to be sold as human food and animal feed5.

In the United States, prevention measures began in 1989 by banning import products from nations where BSE was found. In 1997, the FDA banned ruminant-based protein supplements that were being used as cattle feed6. A USDA inspector will inspect all cattle that are sent out for consumption and any cattle suspected of having BSE are sent for further testing. Due to these stringent restrictions, BSE is prevalent in less than one infected cattle per 1 million. Additionally, most of the vCJD deaths have not occurred in the United States.

The largest known epidemic of mad cow disease occurred in England. 177 people died after contracting variant Creutzfeldt-Jakob disease, whom are believed to have been caused by eating cattle infected with BSE. In 1992 and 1993, 36,680 and 34,370 cattle died due to this disease7. In 2006, a 10 year ban on British beef was finally removed to allow for importation of British beef. After 10 people had died of CJD in 1996, the British government finally acknowledged that people were getting sick off of a variant of BSE. Most cases of CDJ have occurred in the UK with nearly all of them happening between 1980-1996 (Campbell 2006).

Creutzfeldt-Jakob Disease

There are three variations of this disease: variant, sporadic and familial. Variant is caused by the consumption of infected food. Sporadic CJD is what causes the majority of CJD and occurs at random—the trigger for this form is currently unknown. Familial CJD is when a genetic mutation causes the formation of the abnormal prions. This disease has an onset usually in the 45 to 75-year old age group, with peak onset between 60 and 65 years (Collinge 2001). This disease has a high mortality rate, with around 70% of those affected dying within 6 months. In about 1/3 of the cases, patients present symptoms of fatigue, depression, weight loss, headaches and insomnia.


Treatment of prion diseases has thus far been very difficult due to the prions’ resilience towards common sterilization techniques. There have been compounds that inhibit the prion diseases when applied during the inoculation phase, but no treatments have been effective when administered before or during the onset of the disease (Korth et al 2001).

An issue that some medicines have is their ability to bass the blood-brain barrier, which restricts the ability for medicines to reach the central nervous system. There are studies that research which medicines can pass the barrier and inhibit the prions. One such method involves treating the abnormal prion (PrPSc) with tricyclicacridine and phenothiazine derivatives. Phenothiazine are compounds with a tricyclic scaffold and an aliphatic side chain that extends from the middle ring component (Korth et al 2001). Quinacrine, which has been used as an antimaralial drug for over 60 years, is the leading candidate for treatment of patients with variant CJD due to its high potency, but has also been shown to not produce any therapeutic effects. To successfully inhibit PrPSc formation, the ideal amount of carbon atoms in the aliphatic side chain is around 3 to 4. This medicine also suggests the importance of the aliphatic side chain in inhibiting abnormal prion formation. The actual mechanism by which quinacrine and chlorpromazine act on PrPSc is unknown. Other treatments include Congo red, which binds to the β-sheet structures and are believed to act nonspecifically on the PrPSc template by separating the infectious template (Korth et all 2001).

Other methods of treatment involve anti-prion antibodies that can cross the blood-brain barrier. In one study, the researchers were able to grow an anti-prion antibody that was capable of passing the blood-brain barrier in vitro; it also did not display any type of neurotoxic effects.

In a study done by Baxter et al (2005)., they were able to show the effectiveness of radio frequency gas plasma treatment against misfolded prion proteins. In this specific study, the used surgical equipment were treated with gas-plasma to remove residual contamination and they found no apparent damage to the instruments. They were able to reduce residual contamination to levels undetectable by SEM.