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A substantial species barrier prevents chronic wasting disease (CWD), a cervid prion disease with unknown zoonotic potential, from being transmitted to humans, new NIH data suggested.

Healthy human cerebral organoids exposed to high concentrations of CWD inocula from white-tailed deer, mule deer, and elk for 7 days remained uninfected with CWD for up to 6 months, reported Cathryn Haigh, PhD, of the National Institute of Allergy and Infectious Diseases (NIAID) and Rocky Mountain Laboratories in Hamilton, Montana, and co-authors in .

Another prion disease, bovine spongiform encephalopathy (mad cow disease), has transmitted to humans and caused the emergence of variant Creutzfeldt-Jakob disease (CJD), which is widely thought to occur by eating contaminated food. Cases of CJD have risen recently in the U.S. and are universally fatal.

Recently, questions about whether CWD prions could infect humans have emerged. Last month at the American Academy of Neurology annual meeting, researchers from UT Health San Antonio led by Sarah Horn, MD, presented with a history of consuming meat from a CWD-infected deer population, who had rapid-onset confusion and aggression. The man's friend, who also had eaten venison from the same deer population, had recently died of sporadic CJD.

"Based on non-human primate and mouse models, cross-species transmission of CJD is plausible," Horn and colleagues noted, adding that "without detailed prion protein characterization, it is not possible to definitively rule out CWD in these cases."

To date, there is no strong evidence that CWD infects people, . As of February, the condition has been reported in deer, elk, and other animals in at least 32 U.S. states and four Canadian provinces.

"Generally, continual monitoring of CJD cases is required to identify any increase of significance that might indicate CWD has infected humans, especially in CWD-endemic areas," Haigh told 麻豆传媒. "Most cases of CJD are sporadic and rare, so an increase or an emergence of a new variant should be detectable with good monitoring."

CWD is the most transmissible of the prion disease family with highly efficient transmission between cervids. Long-term studies showed using highly sensitive prion disease-screening assays, but identified possible susceptibility in .

To test whether CWD could infect human neural tissue, the NIAID researchers used human cerebral organoids with two different prion genotypes, one of which had previously been shown to be susceptible to zoonotic prion disease. In 2022 and 2023, the team exposed organoids from both genotypes to high concentrations of CWD inocula from three different sources for 7 days and screened periodically for infection for up to 6 months.

No new CWD propagation or deposition of protease-resistant forms of human prions were seen in the CWD-exposed organoids. "Some persistence of the original inoculum was detected, which was equivalent in prion gene knockout organoids and thus not attributable to human prion propagation," the researchers observed.

The findings show that, despite exposure to CWD prions with high infectivity and the capacity to readily become infected with CJD prions, human cerebral organoids were not capable of propagating CWD prions, Haigh and co-authors noted.

This unsuccessful propagation supports a strong species barrier from cervids to humans, they added. "Although we cannot rule out the possibility of CWD crossing into humans, our data suggest that a significant species barrier exists, even when human brain tissue is directly exposed to high-titer CWD brain homogenate for a prolonged period," they wrote.

If any new CWD strains are more infectious than existing ones, NIAID researchers will test them in their organoid system. They also plan to test human gut organoids "because if CWD were ingested in tainted meat we would expect an infection to begin in the gut before reaching the brain," Haigh said.

"We think our findings are good news but we appreciate that it is not possible to predict the future," she added. "Sheep scrapie, another prion disease, has been known of since the 1700s and in that time has not transmitted to humans. We hope this will also be the case for CWD."

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