Scientists Work to Solve Transmission Questions from Mysterious Prion Diseases

Brain Tissue

Brain tissue - with spongy appearance and neuronal loss

To the Fore tribe of New Guinea, cannibalistic funeral practices were believed to return the life force of the deceased to his hamlet. Unbeknownst to them, the custom also brought disease and death to the men, women and children who sometimes cleansed and consumed bodies that were infected with abnormal prion proteins. Kuru, a transmissible spongiform encephalopathy, became endemic to the tribe.

Scientists have been aware of TSEs for more than two centuries – since 1732 with scrapie in sheep and more recently with chronic wasting disease in deer -- though work identifying abnormal prions as the infectious agent continues to evolve. In the 1980s, a marked increase in variant Creutzfeldt-Jakob disease in humans was linked to an outbreak of bovine spongiform encephalopathy (mad cow disease), which spread through cattle in the United Kingdom in an epidemic fashion (most likely due to contaminated feed). TSEs are currently untreatable and always fatal.

For Dr. Edward Hoover, a Professor in the Department of Microbiology, Immunology and Pathology, prion-related diseases were brought to the attention of his laboratory in 1996 when his graduate student Christina Sigurdson became interested in joining the rapidly evolving field.

“Chronic wasting disease, which affects deer, elk and other cervids, was first discovered in Colorado in 1967 and was identified as a TSE in 1978,” said Dr. Hoover. “Since then, the disease has spread to 20 states and continues to be a public health concern. Christina wanted to study prions, which were thought to be the cause of chronic wasting disease, so our laboratory began applying for grants.”

Deer Treatment

Drs. Hoover & Mathiason

The prion protein has a normal and abnormal state. In its abnormal state, the prion is a misfolded protein that is able to convert normal prion molecules into the abnormally structured form. This altered structure accumulates in infected tissue, primarily the brain, causing tissue damage and cell death (the “spongy” architecture of the brain seen in prion-related diseases). The incubation period for TSEs tends to be relatively long, though the disease progresses rapidly once symptoms appear.

Abnormal proteins associated with TSEs have been found in humans, sheep, cervids, cows, cats, some ungulates, and mink. In humans, the most well known TSE disease is Creutzfeldt-Jakob disease, which has a number of variants and various modes of transmission including familial (genetic predisposition), acquired (usually through ingestion of contaminated products or medical interventions such as surgery or blood transfusions where there is prion contamination); and sporadic (no known predisposition or exposure).

“Today, we are working to understand how CWD may be transmitted and have shown that prions can be shed in saliva, urine, feces, and blood,” said Dr. Hoover. “The spread of infection doesn’t require direct animal contact and we’ve shown that infection can spread even in bedding material, soil, and water supplies. We also are studying disease biology, other routes of transmission through non-cervid hosts, genetic predisposition, and immune response.”

Dr. Hoover’s laboratory has developed new diagnostics to test for CWD, and is in a partnership with New York University to investigate a vaccine approach for the prevention of prion-related diseases. As far as the Fore tribe, such an approach may have helped them many years ago, but today the tribe has managed to mostly eradicate kuru through public health initiatives. Changes in Australian law with regards to cannibalistic rituals, and the influence of Christian missionaries on local culture, have resulted in a rapid decline in kuru cases.