Urinary Biomarker Discovered in Variant Creutzfeldt-Jakob Disease

Processed urine samples were mixed with 10% brain homogenate from transgenic mice expressing human prion protein in tubes containing three polytetrafluoroethylene beads and subjected to 96 cycles of PMCA with the use of a Q700 microsonicator (Qsonica; Newtown, CT, USA).

The misfolded prion proteins were detected in the urine of 13 of 14 patients with variant Creutzfeldt-Jakob disease. The single patient whose urine was negative had been receiving an experimental treatment of pentosan polysulfate directly into the brain. No misfolded prion proteins were detected in the urine of any the other study subjects, including the patients who had sporadic Creutzfeldt-Jakob disease. PrPSc was detectable only after extensive amplification by means of PMCA, suggesting that the concentration of the infectious protein in urine is small. Estimations by means of quantitative PMCA suggest that 1 mL of urine obtained from a patient with variant Creutzfeldt–Jakob disease contains as little as 40 to 100 oligomeric PrPSc particles.

Claudio Soto, PhD, the senior author of the study, said, “What could be less invasive than detecting this disease in urine? The fact that we were able to detect just the variant Creutzfeldt-Jakob disease form in the urine is very important. This could lead to the development of commercial technology for diagnosis as well as to determine the safety of donated blood and urinary products.” The study was published on August 7, 2014, in the New England Journal of Medicine (NEJM).

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