1. Prion Diseases Microbes and Society Fall 2007

2. What is a Prion? Prion- small proteinaceous infectious particles which resist inactivation by procedures that modify nucleic acids 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. 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. 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. Appears that the acquisition of PrPsc allows for conversion of PrPc into PrPsc and that leads to disease.

3. Transmissible Spongiform Encephalopathies TSE’s 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) TSE’s 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)

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

5. Animal TSE’s 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? 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 $$$$ CWD- Mostly “scared” hunters. However has the added cost of monitoring which cost $$$$ TME- found in ranched mink so has an impact on fur sales TME- found in ranched mink so has an impact on fur sales

6. More TSE’s and Animals Scrapie- 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. 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. 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. sheep–derived meat and bone meal have been adversely affected. Domestic and international markets for U.S. sheep–derived 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 The combination of all of these factors has led to the decision to develop a strong scrapie eradication program in the United States

7. TSE’s and Humans Creutzfeldt-Jakob Disease (CJD) Creutzfeldt-Jakob Disease (CJD) Variant Creutzfeldt-Jakob Disease (vCJD) Variant Creutzfeldt-Jakob Disease (vCJD) Gerstmann-Straussler-Scheinker Syndrome Gerstmann-Straussler-Scheinker Syndrome Fatal Familial Insomnia Fatal Familial Insomnia Kuru Kuru

8. 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. 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.

9. 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. 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? However, risk of acquiring vCJD through infected cow meat is still low. Why?

10. 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 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. The median duration of illness for vCJD is 14 months, compared to 5 months for classic CJD.

11. 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. 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. 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. 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.

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

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