Prions and the diseases they Cause

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Prions and the diseases they Cause
Kevin Forward
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What are prions

• Proteinaceous infectious particles
• Abnormal proteins that have an affinity for the
  central nervous system and produce degenerative
  diseases.
• The spongiform encephalopathies

• Very highly resistant to heating (survive routine
  autoclaving)
• Not sensitive to irradiation
• Not destroyed by enzymes that damage DNA or RNA
• Sensitive to protein denaturing agents

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What are prions (continues)

• Porins are derived from normal proteins
• The normal proteins are found on the membrane of
  normal cells and are harmless
• By simply folding it differently it is changed
  into a killer
• The abnormal prion proteins fold very differently
  and stick together on the surface of cells and
  produce fibers or fibrils. This damages cells
• The abnormal proteins also cause normal proteins
  to fold differently and they begin to behave like
  abnormal prion proteins

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How are these abnormal proteins acquired?

• A spontaneous occurance
• Inherit an abnormal gene from your parents
• Ingestion of the protein
• Accidentally infection with the protein
  (iatrogenic) Needles, tissue, pituitary extracts

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The Spongiform Encephalopathies

• Human forms
• Creutzfeldt-Jacob Disease
• Sporadic
• Inherited (from a parent)
• Iatrogenic (from a biologic product or device)
• Variant (likely ingested BSE infected cow)
• Kuru
• Animal forms
• Bovine Spongiform Encephalopathy
• Scrapie

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SPORADIC CJD

• The most common form of CJD
• It has been found in every country in the world
  where it has been looked for.
• It affects about one person per million of the
  population.
• The cause of sporadic CJD remains uncertain.
  However, the most favoured current theory
  suggests that the normal prion protein in the
  brain undergoes a spontaneous change to the
  abnormal form, thereby resulting in disease.
• If this theory is correct (and it has not been
  proven at this point) then the disease arises
  simply as a chance event inside the brain. On
  this basis, it would not be "caught" in any way.

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IATROGENIC CJD

• This is CJD which has been accidentally
  transmitted during the course of medical or
  surgical procedures.
• The most important example of this relates to CJD
  transmitted via Human Growth Hormone treatment in
  childhood.
• There are only a few deaths per year due to
  iatrogenic CJD
• The diagnosis is usually clear from the history
  of a relevant medical or surgical treatment in
  the past.

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GENETIC CJD

• Caused by an inherited abnormal gene. The illness
  is therefore not "caught" in any way and there is
  no causal relationship between this form and BSE.
  
• In most cases, the illness is known within the
  family because of the family history.
  Occasionally, genetic cases are seen in which no
  previous family history is identified.
• The United Kingdom has a population of around 58
  million and there are only a few deaths due to
  genetic CJD in a year.

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VARIANT CJD

• Variant CJD was first reported in 1996.
• At this point in time, there are no cases of
  variant CJD with symptoms that began before 1994.
• Aside from 6 cases in France, one case each in
  Ireland, Italy, the USA and Canada, variant CJD
  has been confined to the United Kingdom.
• The current view on variant CJD is that it has
  resulted from transmission of infection from BSE
  in cattle to humans via infectivity in food

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What are the clinical features of
Creutzfeldt-Jacob Disease?

• Progressive dementia
• Asymmetrical weakness and spasticity
• Repetitive jerking movements
• Symptoms may progress to death over weeks or
  months

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CJD and variant CJD are different

• Variant CJD has tended to affect younger
  individuals
• Many cases of variant CJD have durations of a
  year or more (instead of months)
• In variant CJD, the initial presentation is often
  with psychiatric symptoms and it may not be clear
  that the individual has neurological illness
• The neuropathological features of variant and
  sporadic CJD are different.

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Kuru

• Described in the Fore tribe of Papua New Guinea
  in the 1950s.
• Related to ritualistic cannibalism.
• Affected primarily women and their teenage
  children.
• Now no longer seen

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Scrapie

• A disease of sheep and goats
• Known for centuries
• Animals become very uncoordinated and intensely
  itchy (constantly scraping on trees rocks)
• Infected animals served as the source of BSE

Picture from the rear shows bare patches from
rubbing.
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Bovine Spongiform Encephalopathy

• First described in the UK in 1986
• Likely transmitted from scrapie-infected sheep by
  feeding contaminated meat and bonemeal prepared
  from renderings
• A small number of cases have been described in
  Canada. Several have occurred in the United
  States
• Hundreds of thousands of animals were affected
  in the UK.

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How are Prion Diseses Usually Diagnosed ?

• There is no blood test to detect the presence of
  prions or to screen for carriers.
• Currently there are two laboratory methods to
  confirm a diagnosis
• Microscopic examination of the brain tissue to
  identify characteristic changes
• Special staining and microscopic techniques to
  detect the partially-proteinase resistant form of
  the prion (PrPres) protein.

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