The latest research on prion diseases, using a human cerebral organoid model, indicates that there is a significant species barrier that prevents chronic wasting disease (CWD) from cervids such as deer, elk, and moose from being transmitted to humans. These findings align with years of similar research conducted in animal models. The study was conducted by scientists from the National Institutes of Health and was published in Emer.Infectious Diseases, support decades of similar research in animal models at the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
Prion diseases are degenerative diseases found in some mammals. These diseases mainly involve brain degeneration but can also impact the eyes and other organs. Disease and death occur when abnormal proteins fold, clump together, recruit other prion proteins to do the same, and eventually destroy the central nervous system. Currently, there are no preventive or therapeutic treatments for prion diseases.
CWD is a type of prion Disease found in cervids, which are popular game animals. While CWD has never been found in people, a question about its transmission potential has lingered for decades: Can people who eat meat from CWD-infected cervids develop prion disease? The question is important because during the mid-1980s and mid-1990s a different prion disease – bovine spongiform encephalopathy (BSE), or mad cow disease — emerged in cattle in the United Kingdom (U.K.) and cases also were detected in cattle in other countries, including the United States. Over the next decade, 178 people in the U.K. who were thought to have eaten BSE-infected beef developed a new form of prion disease.The emergence of variant Creutzfeldt-Jakob Disease, a human prion disease, resulted in death. Researchers found that the disease had spread from infected prion protein in cattle feed. This transmission path from cattle to people caused fear in the U.K. and raised concerns about other prion diseases transmitted from animals to humans, such as Chronic Wasting Disease (CWD). CWD is the most easily transmitted prion disease, with efficient transmission between cervids.
Historically, scientists have used mice, hamsters, squirrel monkeys and cynomolgus macaques to replicate prion diseases in humans, and have sometimes monitored them.The National Institute of Allergy and Infectious Diseases (NIAID) has been studying animals for signs of Chronic Wasting Disease (CWD) for over ten years. In 2019, NIAID scientists at Rocky Mountain Laboratories in Hamilton, Montana, created a human cerebral organoid model of Creutzfeldt-Jakob Disease (CJD) to test potential treatments and study specific human prion diseases.
Human cerebral organoids are small clusters of human brain cells, ranging in size from a poppy seed to a pea. Scientists cultivate these organoids in dishes using human skin cells. The structure, organization, and electrical signaling of cerebral organoids closely resemble that of brain tissue, making them the closest available laboratory model to the human brain. This new model has the potential to revolutionize the study and treatment of neurodegenerative diseases.Brain organoids, also known as cerebral organoids, can be kept viable in a controlled environment for a long time, making them useful for studying progressive nervous system diseases. These organoids have also been utilized as a tool to investigate various other diseases, including Zika virus infection, Alzheimer’s disease, and Down syndrome.
In a recent study conducted in 2022 and 2023, researchers successfully infected human cerebral organoids with human CJD prions as a way to validate the study model. Following this validation, they exposed healthy human cerebral organoids to high concentrations of CWD prions from white-tailed deer and mule deer for seven days under the same laboratory conditions.The researchers conducted a study using brain organoids derived from human induced pluripotent stem cells. The organoids were exposed to CWD prions, as well as deer, elk, and normal brain matter for comparison. The researchers observed the organoids for up to six months and found that none of them became infected with CWD.
This suggests that there is a significant resistance or barrier to the propagation of infection in human central nervous system tissues even after direct exposure to CWD prions. The researchers acknowledge that their study has limitations, including the possibility of genetic susceptibility that was not considered, and the potential emergence of new strains with a lower barrier to infection. However, they remain optimistic about their findings.It is suggested by the findings of this study that it is highly unlikely for humans to develop a prion disease from consuming meat from CWD-infected deer.
