Researchers have found abnormal prion protein in the skin of 23 people who died from Creutzfeldt-Jakob Disease (CJD). Meanwhile exposing mice to skin tissue taken from the CJD patients caused them to develop prion disease.
The study has raised questions about the possibility of prion diseases being transmitted during medical procedures that involve the skin, as well as the possibility of using skin samples to detect the diseases.
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient’s brain. CJD patients develop signature microscopic sponge-like holes in their brains. The initial signs of CJD include memory loss, behavior changes, movement disorder, and vision problems, which usually rapidly progress to death. According to the National Institutes of Health (NIH), 90 percent of CJD patients die within one year of onset, and hundreds of Americans are diagnosed annually. There is no available treatment or cure.
There are numerous types of prion diseases in humans, and CJD is the most common. About 90 percent of CJD cases have a sporadic origin. Inter-personal CJD transmission has occurred after patients were exposed to surgical tools previously contaminated by CJD brain tissues.
In a Science Translational Medicine study published today, Case Western Reserve University School of Medicine researchers found that CJD patients also harbor infectious prions in their skin, albeit at lower levels. In the study, the researchers collected skin samples from 38 patients with assistance from the National Prion Disease Pathology Surveillance Center at Case Western Reserve School of Medicine and measured their prion levels. Using a highly sensitive in vitro assay developed and conducted by Byron Caughey’s group at the NIH, they detected prion protein aggregates in the skin samples from all of CJD patients. Prion levels were 1,000-100,000 times lower in the skin than in the brain, and only detectable by this extremely sensitive assay. The researchers further demonstrated that such skin prions are infectious, since they are capable of causing disease in humanized mouse models.
“It is well known that CJD is transmissible via surgical or medical procedures involving prion-infected brain tissue. Our finding of infectious prions in skin is important since it not only raises concerns about the potential for disease transmission via common surgeries not involving the brain, but also suggests that skin biopsies and autopsies may enhance pre-mortem and post-mortem CJD diagnosis,” said Wenquan Zou, Associate Professor of Pathology and Neurology and Associate Director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve School of Medicine. Zou led the study involving a consortium of research groups and researchers across Case Western Reserve School of Medicine, University Hospitals Cleveland Medical Center, the NIH, and the People’s Republic of China.
“The level of prion infectivity detected in CJD skin was surprisingly significant, but still much lower than that in CJD brains,” cautioned Qingzhong Kong, Associate Professor of Pathology and Neurology at Case Western Reserve School of Medicine. “Prion transmission risk from surgical instruments contaminated by skin prions should be much lower than that of instruments contaminated by brain tissue.” In the study, the Kong group assisted by the Zou group demonstrated that CJD patient skin is infectious using humanized transgenic mouse models.
Current diagnostic tools for CJD rely on brain tissue samples collected at either biopsy or autopsy, or cerebral spinal fluid obtained by spinal taps. The new study may lay the foundation for less invasive techniques. “Using the skin instead of brain tissue for post-mortem diagnosis could be particularly helpful in cultures that discourage brain autopsy, such as China and India. These countries have the largest populations with the greatest number of patients, but brain autopsy is often not performed,” said Zou.
“Further investigation is necessary to determine whether extra precautions should be taken during non-neurosurgeries of CJD patients, especially when surgical instruments will be reused,” said Zou. Case Western Reserve School of Medicine researchers plan to further evaluate the potential risk of skin prion transmission through non-neurosurgeries, primarily using mouse models.
The study was conducted by scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and various other collaborating groups.
Generally, people associate prion diseases with the brain, although it has been shown that clusters of the abnormal prion protein, which cause sponge-like holes in the brain, can accumulate in other organs including the liver, spleen, lungs and kidney. It is known that Sporadic CJD, which is the most common human prion disease, can be transmitted via invasive medical procedures involving the central nervous system and cornea, but transmission via the skin has not generally been considered a concern.
The authors want to study the risk of surgical instruments becoming contaminated and the risk associated with procedures that involve CJD patients. They also suggest the possibility of using the skin-based diagnostic test for prion diseases in humans and animals.
Gary Chandler is a prion expert. He is the CEO of Crossbow Communications, author of several books and producer of documentaries about health and environmental issues around the world. Chandler is connecting the dots to the global surge in neurodegenerative disease, including Alzheimer’s disease, Parkinson’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and other forms of prion disease. The scientific name for prion disease is transmissible spongiform encephalopathy. The operative word is “transmissible.” Even the global surge in autism appears to be related.