This document describes infectious agents which do not have a nucleic acid genome. It seems that a protein alone is the infectious agent. The infectious agent has been called a prion. A prion has been defined as "small proteinaceous infectious particles which resist inactivation by procedures that modify nucleic acids". The discovery that proteins alone can transmit an infectious disease has come as a considerable surprise to the scientific community.  It is proposed here that Hunza Water has activity against Prions.

What is a Prion?
Evidence suggests that a prion is a modified form of a normal cellular protein known as PrPc (for cellular), a normal host protein encoded by a single exon of a single copy gene. This protein is found predominantly on the surface of neurones attached by a glycoinositol phospholipid anchor, and is protease sensitive. Thought to be involved in synaptic function.
The modified form of PrPc which may cause disease i.e. the prion is known as PrPsc (for scrapie) which is relatively resistant to proteases and accumulates in cytoplasmic vesicles of diseased individuals.

Prion diseases are often called spongiform encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum. Probably most mammalian species develop these diseases. Specific examples include:

1. Scrapie: sheep
2. TME (transmissible mink encephalopathy): mink
3. CWD (chronic wasting disease): muledeer, elk
4. BSE (bovine spongiform encephalopathy): cows

Humans are also susceptible to several prion diseases:
1. CJD: Creutzfeld-Jacob Disease
2. GSS: Gerstmann-Straussler-Scheinker syndrome
3. FFI: Fatal familial Insomnia
4. Kuru
5. Alpers Syndrome

These original classifications were based on a clinical evaluation of a patients family history symptoms and are still widely used, however more recent and accurate molecular diagnosis of the disease is gradually taking the place of this classification.

The incidence of sporadic CJD is about 1 per million per year.  GSS occurs at about 2% of the rate of CJD.  It is estimated that 1 in 10,000 people are infected with CJD at the time of death. These figures are likely to be underestimates since prion diseases may be misdiagnosed as other neurological disorders.

The diseases are characterised by loss of motor control, dementia, paralysis wasting and eventually death, typically following pneumonia. Fatal Familial Insomnia presents with an untreatable insomnia and dysautonomia. Details of pathogenesis are largely unknown.

Visible end results in the brain at post-mortem are non-inflammatory lesions, vacuoles, amyloid protein deposits and astrogliosis.

GSS is distinct from CJD, it occurs typically in the 4th-5th decade, characterised by cerebellar ataxia and concomitant motor problems, dementia less common and disease course lasts several years to death. (Originally thought to be familial, but now known to occur sporadically as well).

CJD typically occurs a decade later.  CJD has cerebral involvement so dementia is more common and patient seldom survives a year (originally thought to be sporadic, but now known to be familial as well).

FFI pathology is characterised by severe selective atrophy of the thalamus at the base of the brain.

Alpers syndrome is the name given to prion diseases in infants.

Scrapie was the first example of this type of disease to be noticed in sheep and has been known about for many hundreds of years.

Humans might be infected by prions in 2 ways:

   1.Acquired infection (diet and following medical procedures such as surgery, growth hormone injections, corneal  transplants) all of which implies that an  infectious agent is implicated.

   2.Apparent hereditary mendelian transmission where it is an autosomal and dominant trait. This is one of the features that single out prion diseases for particular attention.
Prion diseases are both infectious and hereditary diseases. They are also sporadic, in the sense that there are also cases in which there is no known risk factor although it seems likely that infection was acquired in one of the two ways listed above.

 

A new twist in the prion story by Rabiya Tuma, BioMedNet News 25 February 2002 20:27 EST

San Francisco - Reporting at the Biophysical Society meeting here today, California researchers revealed an unpublished new structure for the PrPSc protein. Building on such structural information, scientists are beginning to test compounds that block the transition of the cellular PrPc protein to the disease form, PrPSc. There is one significant difference between the newly proposed structure and previously published ones, said Holger Wille, an electron microscopist at the University of California in San Francisco: In previous structures, the beta-sheets were aligned in an anti-parallel conformation; in this one, the beta-sheets are parallel to one another. The new structure will be published next month in the Proceedings of the National Academy of Sciences. Andrew Robertson, a structural biologist from the University of Iowa in Iowa City, says the difference could have significant implications in the surface properties of the protein and, therefore, in its predicted interactions with other molecules. "The fact that he made such a concrete statement is great," Robertson told BioMedNet News. "There are at least a dozen people in the audience here who will go home and gun at the structure to see if their own data fits the model." Structural studies of PrPSc have been frustrated by the protein's insolubility, a trait required for both NMR and X-ray crystallography techniques, says Wille. But he and his colleagues recently found two-dimensional crystals in protein preparations which are adequate for electron crystallography. The crystals are far from perfect, however. "They are not very nice," Wille acknowledged. But, with the crsytals, "as imperfect as they are, we can still extract quite a bit of information from them by correlation averaging," he said. Wille also obtained crystals of a smaller PrPSc protein, which has a large internal deletion and can still transmit disease. By comparing the crystal structures of the two proteins, he has been able to confirm the location of the beta-sheets, as well as identify several other parts of the protein within the crystal lattice. Fred Cohen, professor of biochemistry and biophysics at UCSF, emphasized the significance of the results. With a better understanding of prion structure and the replication process, he said, scientists are beginning to identify compounds that can interfere with the deadly disease. For example, Cohen's own work builds on structural information about dominant negative mutants of PrPc, the cellular form of the prion protein. These mutants are incapable of forming PrPSc and, even more important, says Cohen, they can inhibit non-mutant forms from taking on the disease structure. Cohen and his colleagues screened a small molecule library for compounds that mimic the critical region of the dominant negative protein, hoping the newly-identified compounds would also mimic the mutant's resistance. The researchers already have numerous compounds, some with binding affinities in the hundred nanomolar range. The best known of these is quinacrine, an old antimalarial drug, which scientists have begun testing in several patients. Cohen declined to comment on the drugs' effectiveness in patients, however. Other compounds in the list include acradine-based molecules, thienopyridines and, most recently, bis-quinacrines. "We believe that we are beginning to see some compounds that can interfere with prion replication," Cohen said. "This is a useful first step in doing something about the knowledge we gained." Picture caption and credit: Conformation of prion protein as determined through magnetic resonance spectroscopy; National Coordination Office for Information Technology Research and Development. For live daily reports from BPS 2002, go to Conference Reporter. NEWS  April 6, 2002 Prion-Disease Trials on the Horizon? Prusiner reports on progress of research By Jennifer Fisher Wilson The discoverer of prions, the pathogens implicated in the fatal, brain-wasting mad cow disease (bovine spongiform encephalopathy, BSE) and Creutzfeldt-Jakob disease (CJD), announced recently that a therapy against them would likely be available within the next five to 10 years, but he added that scientists are still mystified by exactly what circumstances cause the pathogens to produce infections in animals and humans. "We thought that the number of cases of the disease would increase two to three times, but the number of cases in 2001 was similar to the number in 2000," Stanley B. Prusiner, 1997 Nobel Prize winner, told a crowded room of scientists at the University of Pennsylvania on Feb. 13. Prion diseases are difficult to predict, he said, because they involve so many variables. For example, it is still unknown why the new variant form of CJD disease, caused by BSE, is confined to young people while inherited CJD, also known as sporadic CJD, afflicts only the aged, he said. All the same, after almost 20 years researching prions, "I think we now know enough about these diseases to really mount a program that hopefully will give us a therapy," said the neurologist and biochemist who directs the University of California, San Francisco, Institute for Neurodegenerative Diseases. The most promising finding so far, Prusiner reported, comes from studies with two older tricyclic compounds: quinacrine, approved to treat malaria and giardiasis, and chlorpromazine, approved to treat schizophrenia and other psychotic conditions.1 The structure of these compounds—three-ring scaffolding with side chain of molecules extending off a central section—appears to be critical to the drugs' ability to inhibit the conversion of normal prion protein into the disease-causing form. Preliminary trials using quinacrine in patients with both new variant CJD and sporadic CJD apparently reduced symptoms early in treatment but failed to cure the disease, according to Prusiner. He stated that he is currently obtaining funding for a larger, controlled trial and is working on a mouse model for testing the therapies, as well. He also noted plans to initiate a drug discovery program to search through about 11,000 compounds over the next five years for any that might be more efficacious than quinacrine or chlorpromazine. Prusiner reported on the status of his ongoing prion research at the first annual Nathanson Lectureship, which honors Neal Nathanson, a leader in the field of viral pathogenesis and current vice provost for research at Penn. Jennifer Fisher Wilson (jfwilson@aol.com) is a contributing editor. 1. C. Korth et al., "Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease," Proceedings of the National Academy of Sciences, 98:9836-41, 2001.

Site Map for colloidal water science

Disclaimer: The information conveyed here is based on records and research for your information which is for horticultural, educational, sacramental and research purposes only.  No statement should be taken as medical advice.  It is not claimed or implied here that Mono-atomic SILVER-MAX or Colloidal mineral waters will cure any disease.

Contact:  Biophysica Inc., Toronto, Ont, Canada M6R 1S5 Phone: (905) 827-9448 (10am to 10pm EST)

e-mail: info@biophysica.com

Copyright 2001, Biophysica Inc. All rights reserved. Powered by Stonix.com.     

This page last updated on July18, 2005

Back to Home Page