Prion Diseases

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Prion Diseases

• Microbes and Society
• Fall 2007

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What is a Prion?

• Prion- small proteinaceous infectious particles
  which resist inactivation by procedures that
  modify nucleic acids
• Disease causing prion is a modified form of a
  normal cellular protein known as PrPc. This
  normal form is protease sensitive so it does not
  accumulate.
• The modified prion is known as PrPsc (for
  scrapie) which is relatively resistant to
  proteases and accumulates in cytoplasmic vesicles
  of diseased individuals.
• Appears that the acquisition of PrPsc allows for
  conversion of PrPc into PrPsc and that leads to
  disease.

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Transmissible Spongiform Encephalopathies

• TSEs are a family of rare progressive
  neurodegenerative disorders that affect both
  humans and animals. They are distinguished by
  long incubation periods, characteristic
  spongiform changes associated with neuronal loss,
  and a failure to induce inflammatory response.
  (CDC)

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TSEs in Animals

• Scapie- sheep, first known TSE been around for
  100s of years. Sheep get it by ingestion off of
  pasture or transplacental transmission
• Mad Cow Disease or BSE- cows. First cases may
  have occurred by feeding scrapie infected tissue
  to cows
• Chronic Wasting Disease (CWD)- deer, elk
• Transmissible Mink Encephalopathies (TME)- mink

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Animal TSEs and Society

• BSE in Great Britain cost millions of dollars,
  loss of life, a crash in the beef industry and
  fostered mistrust of the government. Others?
• CWD- Mostly scared hunters. However has the
  added cost of monitoring which cost
• TME- found in ranched mink so has an impact on
  fur sales

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More TSEs and Animals

• Scrapie-
• Packers and producers have had difficulty finding
  options for disposal of sheep offal and dead
  sheep causing packers and producers to incur
  significant increases in disposal costs.
• Other countries have expressed concerns and
  have indicated that they may prohibit or restrict
  certain ruminant products because the United
  States has scrapie.
• Domestic and international markets for U.S.
  sheepderived meat and bone meal have been
  adversely affected.
• The combination of all of these factors has led
  to the decision to develop a strong scrapie
  eradication program in the United States

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TSEs and Humans

• Creutzfeldt-Jakob Disease (CJD)
• Variant Creutzfeldt-Jakob Disease (vCJD)
• Gerstmann-Straussler-Scheinker Syndrome
• Fatal Familial Insomnia
• Kuru

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Classic CJD

• Classic CJD has been recognized since the early
  1920s. The most common form of classic CJD is
  believed to occur sporadically, caused by the
  spontaneous transformation of normal prion
  proteins into abnormal prions. This sporadic
  disease occurs worldwide, including the United
  States, at a rate of approximately one case per 1
  million population per year, although rates of up
  to two cases per million are not unusual.

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vCJD

• There is now strong scientific evidence that the
  agent responsible for the outbreak of prion
  disease in cows, BSE, is the same agent
  responsible for the outbreak of vCJD in humans.
  Both disorders are invariably fatal brain
  diseases with unusually long incubation periods
  measured in years, and are caused by an
  unconventional transmissible agent.
• However, risk of acquiring vCJD through infected
  cow meat is still low. Why?

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Comparison of classic CJD and vCJD

• The median age at death for vCJD patients is 28
  years, compared with 68 years for patients with
  classic CJD.
• The median duration of illness for vCJD is 14
  months, compared to 5 months for classic CJD.

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Kuru

• Kuru is a rare and fatal brain disorder that
  occurred at epidemic levels during the 1950s-60s
  among the Fore people in the highlands of New
  Guinea.
• The disease was the result of the practice of
  ritualistic cannibalism among the Fore, in which
  relatives prepared and consumed the tissues
  (including brain) of deceased family members.
• Brain tissue from individuals with kuru was
  highly infectious, and the disease was
  transmitted either through eating or by contact
  with open sores or wounds.

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Inherited Human TSEs

• Gerstmann-Straussler-Scheinker Syndrome- a rare
  inherited dementia that presents in the later
  years.
• Fatal Familial Insomnia- an extremely rare
  inherited prion disease that is characterized by
  insomnia and ultimately death.

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Treatment

• Nothing yet, but immune cells may be what carries
  the protein to the lymph nodes and eventually the
  brain.
• Prevention- food animals have strict diets which
  limit or prevent animals from ingesting CNS
  material that may contain prions.