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.

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.

Tests are planned, based on research grant availability, to determine the range of effectiveness of Antivirol against prions.