P
Anton Sebastian in A Dictionary of the History of Medicine, 2018
Prion Disease (Syn: spongiform encephalopathy) Disorders of protein conformation that produce neurodegeneration in humans and animals. Scrapie has been known in sheep for over 200 years. Creutzfeld-Jakob disease was described by Hans Gerhard Creutzfeld (1885–1964) in 1920 and Alfons Maria Jakob (1884–1931) in 1921. Kuru was first observed by an American virologist, Daniel Carleton Gajdusek (b 1923) and V. Zigas in 1957. Kuru, scrapie and Creutzfeld-Jakob disease were recognized to be infectious in the 1960s. Spongiform bovine encephalopathy of cattle (BSE) was recognized in England in 1986 and is the result of feeding cattle with meat and bonemeal from sheep infected with scrapie. Such feeding of ruminant-derived proteins to ruminants was banned in England in 1988. After a peak in the BSE epidemic in 1993 the incidence has fallen, consistent with an incubation period of 5 years. Other diseases in the group, such as Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia were described between 1990–1995.
Introduction
Kiheung Kim in The Social Construction of Disease, 2006
On 6 October 1997, the Nobel Assembly at the Karolinska Institute announced the award of the Nobel Prize in Physiology or Medicine for 1997 to Stanley Prusiner for his discovery of ‘Prions – a new biological principle of infection’ (Karolinska Institute 1997). The Nobel Committee explained that Prusiner had added prions to the list of well-known infectious agents, including bacteria, viruses, fungi and parasites. According to Prusiner, a prion is not a virus or a bacterium, but a protein devoid of nucleic acids and RNA. Prions were held to be responsible for a category of diseases that has become known as transmissible spongiform encephalopathies (TSEs) or prion diseases, including scrapie (sheep and goats), bovine spongiform encephalopathy (known as BSE or ‘mad cow disease’ in cattle), transmissible mink encephalopathy (mink), chronic wasting disease (deer), kuru (humans), Creutzfeldt–Jakob disease (humans), Gerstmann–Straussler–Scheinker syndrome (humans) and fatal familial insomnia (humans). After the novel theory of infection was suggested in Science in 1982 (Prusiner 1982a), the scientific community entered a long period of controversy. The prion theory was denounced by many scientists as ‘heretical’, because it suggested that the agent was proteinaceous in nature; it was therefore seen as a direct challenge to the conventional wisdom of molecular biology, according to which only nucleic acids could embody and transfer information. Subsequently, influential sections of the wider scientific community gradually accepted Prusiner's once-heretical idea. Nevertheless, throughout the 1980s and 1990s, the two opposite scientific camps failed to reach agreement on the meaning of their scientific results.
Micronutrients in the Management of Prion Disease
Kedar N. Prasad in Micronutrients in Health and Disease, 2019
Prion diseases are a group of rare, progressive, transmissible, incurable, and fatal neurodegenerative diseases. They are characterized by transmissible spongiform encephalopathy (TSE) and are found in mammals, including humans. In 1730’s, the symptoms of prion disease were known as scrapie in sheep and goat. In 1957, a transmissible neurological disease called Kuru, similar to Creutzfeldt-Jakob disease (CJD), was identified in the Fore tribe of Papua, New Guinea.1 Extracts from the autopsied brain samples of individuals with Kuru when administered into chimpanzees led to similar brain pathology.2 A similar cross-species infectivity was found in the United Kingdom following an outbreak of “mad cow disease.” In 1982, Dr. Stanley Prusiner of the University of California School of Medicine, San Francisco, proposed the term “prion” because pathogenic misfolded normal prion proteins caused this disease. He isolated an infective agent from the brain of sheep with scrapie and bovine spongiform encephalopathy (BSE) in cattle that causes neurodegeneration in sheep and goats.3 A similar infectious agent was isolated from brains of victims of the genetic diseases Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome (GSS). In 2012, a novel idea suggested that neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease could be considered a prion disease.4 This view was questioned because the similarity between beta-sheet of Aβ peptides of AD and their aggregation characteristics and the characteristics of PrPsc in producing neurodegeneration is not sufficient to support this suggestion.5 Beta-sheet Aβ peptide of AD does not replicate, but PrPsc of prion disease does.
Ultrasensitive techniques and protein misfolding amplification assays for biomarker-guided reconceptualization of Alzheimer’s and other neurodegenerative diseases
Published in Expert Review of Neurotherapeutics, 2021
Nicole Campese, Maria Francesca Beatino, Claudia Del Gamba, Elisabetta Belli, Linda Giampietri, Eleonora Del Prete, Alessandro Galgani, Andrea Vergallo, Gabriele Siciliano, Roberto Ceravolo, Harald Hampel, Filippo Baldacci
Prions are currently recognized as the pathogenic agent of some fatal rapidly progressive NDDs collectively called prion diseases or transmissible spongiform encephalopathies. In humans, these include Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker syndrome, and fatal familial insomnia [32]. Although some instrumental findings (e.g. magnetic resonance imaging – MRI, electroencephalography – EEG and CSF findings) support a clinical diagnosis of prion disease, a definite one relies on the neuropathological examination or on the demonstration of PrPsc in brain tissue by means of immunoblotting or immunohistochemical techniques [33–35]. Recently, the introduction of novel ultrasensitive seeding amplification assays has enabled the in vivo detection of PrPsc in CSF with sensitivity ranging for RT-QuIC from 80–90% for the first-generation [36,37] to 92–96% for the second-generation assays and 98–100% specificity [38,39]. In the olfactory mucosa RT-QuIC is able to detect prion proteins with a sensitivity ranging from 97% [32] to 100% (when combined with CSF RT-QuIC) respectively and 100% specificity [40] with 98–100% of concordance both in CSF and in the olfactory mucosa between different laboratories [41]. At last, RT-QuIC has been applied to skin, showing diagnostic sensitivity and specificity close to 100% in sporadic CJD (sCJD) [42].
Tackling prion diseases: a review of the patent landscape
Published in Expert Opinion on Therapeutic Patents, 2021
Marco Zattoni, Giuseppe Legname
Human prion diseases are etiologically divided into idiopathic, genetic, and acquired. Among the idiopathic forms, which accounts for the majority of prion diseases cases, there are sporadic Creutzfeldt-Jakob disease (sCJD) and variably protease-sensitive prionopathy. Genetic prion diseases, such as, fatal familial insomnia, genetic CJD and Gerstmann-Sträussler-Scheinker syndrome are characterized by autosomal dominant mutations in human PRNP gene. The acquired forms are very rare and account for ritual cannibalism, as Kuru, contamination through surgical instruments, as in the case of iatrogenic CJD, or consumption of animal products contaminated with the agent responsible for the bovine spongiform encephalopathies (BSE) [7]. The BSE epidemic, often referred to as ‘mad cow disease,’ has attracted the attention of the public health authorities and the scientific community since it was shown to cause a new variant form of Creutzfeldt-Jakob disease (vCJD) in humans [8,9]. Besides BSE, other prion diseases discovered in animals include scrapie in sheep and goats and chronic wasting diseases (CWD) in cervids, for which no transmission to humans has been shown so far, although their potential risk cannot be dismissed [10,11]
The cellular prion protein and its derived fragments in human prion diseases and their role as potential biomarkers
Published in Expert Review of Molecular Diagnostics, 2019
Katrin Thüne, Matthias Schmitz, Anna Villar-Piqué, Hermann Clemens Altmeppen, Markus Schlomm, Saima Zafar, Markus Glatzel, Franc Llorens, Inga Zerr
In humans, prion diseases appear in three principal forms: 1) sporadic forms mostly manifesting as sporadic Creutzfeldt-Jakob disease (sCJD), 2) inherited forms manifesting as genetic CJD (gCJD), fatal familial insomnia (FFI), or Gerstmann-Sträussler-Scheinker syndrome (GSS), and 3) forms acquired by infection/transmission including iatrogenic CJD cases, kuru and variant CJD (vCJD). Human prion diseases present with a wide-ranging clinical heterogeneity including rapidly progressive dementia, motor dysfunction, cerebral ataxia, myoclonus and insomnia [85–87].
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