NIH study shows chronic wasting disease unlikely to jump from animals to humans

Media Advisory

Friday May 17, 2024

Study of brain organoids strengthens evidence for a significant barrier between species

WHAT:

A new study of prion diseases, using a human brain organoid model, suggests that there is a significant species barrier preventing the transmission of chronic wasting disease (CWD) from cervids (deer, elk and moose) to humans. The results, from scientists at the National Institutes of Health and published in Emerging infectious diseasesare consistent with 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 certain mammals. These diseases primarily involve deterioration of the brain but can also affect the eyes and other organs. Illness and death occur when abnormal proteins misfold, clump together, recruit other prion proteins to do the same, and eventually destroy the central nervous system. There is currently no preventative or therapeutic treatment for prion diseases.

CWD is a type of prion disease found in deer, a popular game animal. Although CWD has never been detected in humans, a question about its transmission potential has persisted for decades: Can people who eat meat from CWD-infected deer develop prion disease? The question is important because in the mid-1980s and mid-1990s, another prion disease – bovine spongiform encephalopathy (BSE) or mad cow disease – emerged in cattle in the United Kingdom (UK). and cases have also been detected in cattle in other countries. countries, including the United States. Over the next decade, 178 people in the United Kingdom, suspected of having eaten BSE-infected beef, developed a new form of human prion disease, variant Creutzfeldt-Jakob disease, and were deceased. Researchers later determined that the disease had spread among cattle through feed contaminated with an infectious prion protein. The way the disease is transmitted, from feed to livestock to humans, has terrified UK residents and put the world on alert for other prion diseases transmitted from animals to humans. men, particularly CWD. CWD is the most transmissible of the prion disease family, demonstrating very efficient transmission between deer.

Historically, scientists have used mice, hamsters, squirrel monkeys and cynomolgus macaques to mimic prion diseases in humans, sometimes monitoring the animals for signs of CWD for more than a decade. In 2019, NIAID scientists at Rocky Mountain Laboratories in Hamilton, Montana, developed a human brain organoid model of Creutzfeldt-Jakob disease to evaluate potential treatments and study specific human prion diseases.

Human brain organoids are small spheres of human brain cells that range in size from a poppy seed to a pea. Scientists grow organoids in dishes from human skin cells. The organization, structure, and electrical signaling of brain organoids are similar to those of brain tissue. It is currently the closest laboratory model available to the human brain. Because organoids can survive in a controlled environment for months, scientists use them to study diseases of the nervous system over time. Brain organoids have been used as models to study other diseases, such as Zika virus infection, Alzheimer’s disease and Down syndrome.

In the new CJD study, the majority of which was carried out in 2022 and 2023, the research team validated the study model by successfully infecting human brain organoids with human CJD prions (positive control ). Then, using the same laboratory conditions, they directly exposed healthy human brain organoids to high concentrations of CWD prions from white-tailed deer, mule deer, elk, and normal brain matter for seven days ( negative control). The researchers then observed the organoids for six months, and none became infected with CWD.

This indicates that even after direct exposure of human central nervous system tissues to CWD prions, there is substantial resistance or barrier to the spread of infection, according to the researchers. The authors acknowledge the limitations of their research, including the possibility that a small number of people have a genetic susceptibility that has not been taken into account and that the emergence of new strains with a lower barrier to infection remains possible. . They are optimistic that the conclusion from this current data is that it is extremely unlikely that humans will contract prion disease due to inadvertently consuming meat from CWD-infected deer.

ARTICLES:

B Groveman and K Williams and others. Lack of transmission of chronic wasting disease prions to human cerebral organoids. Emerging Infectious diseases DOI: 10.3201/eid3006.231568 (2024).

B Groveman and NC Ferreira and others. Human brain organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease. Scientific reports DOI: 10.1038/s41598-021-84689-6 (2021).

Race B et al. Absence of transmission of chronic wasting disease to Cynomolgus macaques. Journal of Virology DOI: 10.1128/JVI.00550-18 (2018).

Race B and others. Susceptibilities of nonhuman primates to chronic wasting disease. Emerging infectious diseases DOI: 10.3201/eid1509.090253 (2009).

WHO:

Cathryn Haigh, Ph.D., chief of the Prion Cell Biology Unit at NIAID’s Neurological Infections and Immunity Laboratory, is available to comment on this study.

NIAID conducts and supports research – at the NIH, across the United States and around the world – to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose and treat these diseases. NIAID-related press releases, fact sheets, and other materials are available on the NIAID website.

About the National Institutes of Health (NIH):The NIH, the nation’s medical research agency, is comprised of 27 institutes and centers and is part of the U.S. Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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