# Role of skin prions in disease transmission and diagnostic testing of human prion disease

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $585,982

## Abstract

ABSTRACT
Prions (or PrPSc) are the causal agents of fatal transmissible prion diseases including sporadic
Creutzfeldt-Jakob disease (sCJD, the most common human prion disease) in humans as well as
scrapie, mad cow disease and chronic wasting disease in animals. sCJD is transmissible via medical or
surgical procedures due to contamination by abundant infectious prions in the brain of patients. Notably, some
epidemiological studies have also associated sCJD risk with non-neurosurgeries but experimental evidence
for such a link is lacking. sCJD is currently incurable. At the onset of clinical symptoms, permanent brain
damages already occurred. The absence of less invasive early diagnostic tests for the disease can result in
missing the critical window for future treatments, and low brain autopsy rate due to cultural constraints
prevents the surveillance of sCJD that is essential for effective prevention of iatrogenic sCJD
transmissions. Our recent study using the highly sensitive real-time quaking-induced conversion (RT-
QuIC) assay and humanized transgenic (Tg) mice-based bioassay revealed that the skin of sCJD
patients harbors infectious prions (Orrú et al., 2017). Our new preliminary results further indicate that skin
PrPSc is detectable by both RT-QuIC and serial protein misfolding cyclic amplification (sPMCA) assays even
at the asymptomatic stage in a prion-infected animal model. We hypothesize that skin PrPSc can be both
a source of iatrogenic prion transmission and a biomarker for preclinical/premortem/postmortem
diagnostic testing of prion diseases. To test for the hypothesis, the following four Aims will be pursued:
(1) to quantitate infectivity of skin prions from sCJD patients, (2) to pinpoint the distribution of PrPSc within the
skin, (3) to evaluate the potential of skin PrPSc as the source of iatrogenic transmission, and (4) to validate
skin PrPSc as a biomarker for diagnosis of prion diseases. We expect that the proposed study will not only
shed light on the potential risk of human-to-human sCJD transmission via skin prions but also establish
alternative preclinical/premortem/postmortem diagnostic assays for prion diseases. Moreover, new
knowledge generated from this study may apply to much more common neurodegenerative diseases such
as Alzheimer’s and Parkinson’s diseases where the disease-specific misfolded proteins have been
observed in the skin of respective patients.

## Key facts

- **NIH application ID:** 10260502
- **Project number:** 5R01NS109532-04
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** QINGZHONG KONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $585,982
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260502

## Citation

> US National Institutes of Health, RePORTER application 10260502, Role of skin prions in disease transmission and diagnostic testing of human prion disease (5R01NS109532-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10260502. Licensed CC0.

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