Researchers have successfully used two methods to detect prions in skin samples collected from inoculated rodents. The study provides the first proof-of-concept evidence that readily accessible skin samples could be used to detect prion disease early — before clinical symptoms appear.
In the new study, they successfully detected prions in rodent skin samples as early as two weeks post-infection. They also detected prions in the skin of uninoculated rodents that were housed alongside inoculated cage mates, demonstrating that prion transmission can occur between cohabitating rodents.
Prions were detected in skin samples from the inoculated rodents before they showed any clinical signs of prion disease. The researchers first inoculated the brains of hamsters and humanized transgenic mice with rodent or human prion samples, respectively. Then, they collected skin and brain samples at different time points and used two different methods to detect disease-associated prion proteins in the tissues. In both hamsters and mice, the researchers detected prions in skin before they could be detected in brain tissue. The researchers concluded that skin prions could serve as a useful biomarker for preclinical diagnosis of prion diseases.
The study compared two highly-sensitive prion detection methods: RT-QuIC (real-time quaking-induced conversion) and sPMCA (serial protein misfolding cyclic amplification). Both assays were able to efficiently amplify trace amounts of disease-associated prion protein found in the skin tissues of infected animals. The tests use prions in tissue samples as a template and either normal brain tissue or synthetic prion protein as “building blocks” to dramatically amplify minute amounts of prions to detectable levels.
The study results build upon previous work showing that autopsy skin samples from human prion disease patients exhibit prion seeding and infectivity. The next step will be to develop and validate the skin prion tests for clinical use. The researchers believe the methods may also be adapted for diagnosis of other diseases involving misfolded proteins.