Wenquan Zou, MD, PhD Associate Professor Departments of Pathology and Neurology Director of CJD Skin Project Associate Director National Prion Disease Pathology Surveillance Center Institute of Pathology Case Western Reserve University School of Medicine Cleveland, Ohio 44106

Prions from Brain Detectable in Skin Earlier Than Brain Damage

MedicalResearch.com Interview with:

Wenquan Zou, MD, PhD Associate Professor Departments of Pathology and Neurology Director of CJD Skin Project Associate Director National Prion Disease Pathology Surveillance Center Institute of Pathology Case Western Reserve University School of Medicine Cleveland, Ohio 44106

Dr. Wen Quan Zou

Wenquan Zou, MD, PhD
Associate Professor
Departments of Pathology and Neurology
Director of CJD Skin Project
Associate Director
National Prion Disease Pathology Surveillance Center
Institute of Pathology
Case Western Reserve University School of Medicine
Cleveland, Ohio 44106

MedicalResearch.com: What is the background for this study?

Would you briefly explain the significance of prion-induced diseases and why they have been difficult to diagnosis?

Response: Our previous study has demonstrated that infectious prions are detectable in the skin samples of patients with sporadic Creutzfeldt-Jakob disease (sCJD), the most common form of human prion disease, at the terminal stage by the highly sensitive real-time quaking-induced conversion (RT-QuIC) assay and animal-based bioassay.

The prion-induced diseases are significant because they are infectious diseases that can be transmitted inter-species and intra-species. For instance, mad cow disease, a prion disease in cattle, has been documented to transmit to humans. Currently, there are no cures for these fatal diseases.

The definite diagnosis of prion diseases is difficult because it mainly depends on the availability of brain tissues obtained either by biopsy or autopsy for detection of prions. Brain biopsy is highly invasive and it is difficult to be accepted by patients and their families. Even for brain autopsy, it is not always feasible because of religious and cultural limitations in some regions or countries. 

MedicalResearch.com: What are the main findings?

Response: The main findings in our current study are that the prions generated in the brain are detectable in skin tissue far earlier than the prion-caused brain damage, and that normal animals may obtain the infection via co-habitation with infected animals.

These findings are important because it may open a new avenue for prevention of the disease or for efficient treatment. It is known that once the brain cells are injured, the damage is often irreversible, which could be one of the reasons why so far no compounds have been proven to be effective. So, a strategy to prevent prion-induced brain damage may be developed if the disease can be diagnosed in the skin samples before brain damage occurs.

In addition, there are no epidemiological data supporting the possibility that prion disease is transmissible by co-habitation in humans. However, there is evidence that it could happen in animal prion diseases such as scrapie in sheep and goats as well as chronic wasting disease in elk and deer. Our finding of prion transmission via co-inhabitation suggests that skin may play a role in transmission of animal prion diseases. 

MedicalResearch.com: What should readers take away from your report?

Response: The take away from our study is that skin prions could be a biomarker for early preclinical diagnosis of prion diseases. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We are going to use the highly sensitive RT-QuIC and sPMCA assays to develop premortem diagnostic tools for CJD patients by examining their skin biopsy samples. To verify that our skin-based approaches are able to be used for early preclinical detection of prions in CJD patients, it is necessary to conduct a longitudinal study in asymptomatic prion protein mutation carriers to find out how early we can detect skin prions before the mutation-carriers show clinical signs and symptoms. It would be also important to further determine what role the skin may play in the interspecies transmission of animal prion diseases such as scrapie and mad cow disease. 

MedicalResearch.com: Is there anything else you would like to add?

Response: Unlike patients with Parkinson’s disease who may have prodromal non-motor symptoms and signs such autonomic disturbances, olfactory dysfunctions, depression and sleep disorders, no prodroma have been identified in patients with sporadic CJD. Once patients with sCJD show clinical symptoms, they are not early stage and already experienced significant brain damage. It is most likely that the skin-based longitudinal follow-up study of prion protein mutation-carriers may offer us a chance to identify those prodromal signs and symptoms in these individuals, which could also be applicable to sporadic CJD patients.

Like prion diseases, misfolded alpha-synuclein and tau protein associated with Parkinson’s disease and Alzheimer’s disease, respectively, also have been reported in skin tissues of patients with these conditions. Thus, it is most likely that skin could serve as a mirror not only for early diagnosis, but also for monitoring the accumulation of the misfolded proteins in the brain of these neurodegenerative diseases.

Citation:

Zerui Wang, Matteo Manca, Aaron Foutz, Manuel V. Camacho, Gregory J. Raymond, Brent Race, Christina D. Orru, Jue Yuan, Pingping Shen, Baiya Li, Yue Lang, Johnny Dang, Alise Adornato, Katie Williams, Nicholas R. Maurer, Pierluigi Gambetti, Bin Xu, Witold Surewicz, Robert B. Petersen, Xiaoping Dong, Brian S. Appleby, Byron Caughey, Li Cui, Qingzhong Kong, Wen-Quan Zou. Early preclinical detection of prions in the skin of prion-infected animals. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-018-08130-9

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Feb 1, 2019 @ 11:59 am

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1 Comment
  • Linda Yvette Eichfeld
    Posted at 00:00h, 04 February Reply

    Hi. I am currently attending school and I look forward to a career in studying Prions. I still have a way to go with my education, however. I have been extremely interested in the type of bonding Prions exhibit. I know that Prions have a negative charge at one end of the molecule . I think it is a t the N- terminus. Is this what binds to the outside of a healthy cell when a “conformation” takes place? Or, is this a question that still cannot be answered yet? Also, I do not find it possible that Prions do not contain DNA or RNA. I said, “I do not”. I am NOT a scientist (yet!) but, how can any disease spread it self without DNA or RNA?? It just does not seem realistic. The words, “confirmation ” and “domino effect” are thrown around when an organization or medical school puts out an article on how the Prions affect the host cell. No one knows how these proteins go “rouge”.There is still no answer about how these proteins change. I am just not satisfied with these terms used. There needs to be an answer , and I am going to find out.

    Linda Y. Eichfeld

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