W1 - Introduction to protein misfolding diseases

What is the energy difference between folded and non-folded proteins?

~ 5-15 kcal/mol

Give 3 examples of protein misfolding diseases

• prion “mad cow”

• alzheimer’s

• parkinsons

What is amyloidosis?

rare group of diseases characterised by the buildup of abnormal proteins (amyloids) in various organs

Describe the neuropathology of prion diseases

spongiform degeneration of the CNS. Protein aggregates and amyloid plaques are seen, which are resistant to proteolytic degredation.

List 3 things that prion diseases can be

• inheritable (autosomal dominant)

• infectious

• sporadic

Give one example of a sporadic prion disease

Creutzfeldt - Jakob Disease (CJD)

What percentage of prion diseases are CJD?

85%

When does CJD present in life?

the 6th century

List 2 symptoms of CJD

dementia and ataxia (tremors)

Give 3 examples of inheritable prion diseases

• Gertsmann-Straussler-Schneider disease

• familial CJD

• Fatal Familial Insomnia (FFI)

Give two examples of infectious prion diseases (TSE’s)

• Kuru

• Iatrogenic CJD

Which group of people did kuru affect?

the fore-tribes-people in New Guinea

How was kuru contracted?

ritualistic cannibalism, specifically due to consumption of the brain

What is the incubation time for kuru?

5 & 30 years

How soon did most people that contracted kuru die?

from the first symptoms most die within a year

How many deaths were counted by kuru and when?

2584 deaths between 1958 and 1982

What does Iatrogenic mean?

illness caused by medical examination / treatment

List 3 ways that iCJD can be contracted?

• injection of HGH derived from pituitary glands

• cornea and other grafts

• surgical instruments

How many deaths were caused by iCJD transmitted by injection of HGH?

90

How long was incubation for iCJD transmitted by injection of HGH?

between 3 and 20 years

How many deaths were caused by iCJD transmitted by grafts?

60

How long was incubation for iCJD transmitted by grafts?

between 1-14 years

List a common pathology of TSE’s

protein deposits form extracellular plaques, packing of fibers can generate cross shapes

List 3 transmissible spongiform encephalopathies

• scrapie in sheep

• chronic wasting disease in canada deer

• BSE / mad cow disease

Scrapie (3 points)

• existed in sheep all around the world

• infectious but certain breeds are more prone

• not zoonotic

Chronic wasting disease

aka “zombie deer disease” (moose, deer, and elk)

When was the height of BSE and how many cases per week were reported

1992, 1,000 cases per week

How many cattle deaths were recorded as a result of BSE?

>160,000

How many cattle were estimated to be infected with BSE?

1 million

What was the mean incubation time of BSE, and when were cattle slaughtered in their lifetime?

5 years, slaughtered at 2-3 years

What was BSE caused by?

a change in the rendering process in Britain in the late 70’s

What was initial infection of BSE caused by?

meat and bone meal (MBM) of sheep, further infection from MBM of cows

What was the rough gross cost of cattle slaughter?

£5.5 billion

What other animals were infected by BSE following the consumption of MBM?

mink, mules, deer and cats

Sunday times, May 1990

Leading food scientist calls for slaughter of 6 million cows. The UK government didn’t agree with him and he was accused of fear mongering

John Gummer

an agricultural minister, fed his daughter a beef burger to indicate how sure he was that BSE wasn’t an issue

December 1995

“there is no conceivable risk of BSE being transmitted from cows to people” - Steve Dorrell, Minister of State for Health

The Times 1996

infected macaque monkeys with BSE, the pathology that was produced in their brains was very similar to that found within patients that had died with new variant CJD

Daily mirror, 1996

“mad cow can kill you, government to admit it today. We have already eaten 1,000,000 mad cows”

October 1996

the EU banned imports of British beef. Mcdonalds pulled British big macs from its menu

How many cases a week were reported by 2007?

~5

Where was vCJD obsered?

in the UK and France

What demographic is vCJD more likely to affect?

teens and young adults

when was the first case of vCJD reported?

1995

How many cases of vCJD were reported in 1997, 1999, and 2000?

10, 16, 30

What was vCJD linked to?

infected beef and the mad cow epidemic

How many total deaths were recorded as a result of vCJD?

200

List 2 ways that vCJD could be transmitted

• mother to baby transmission

• blood transfusion transmission