Urinary Biomarker Discovered in Variant Creutzfeldt-Jakob Disease

The misfolded and infectious prion protein that is a marker for variant Creutzfeldt-Jakob disease has been detected in the urine of patients with the disease.

There are currently no noninvasive tools available to diagnose the disease which is linked to the consumption of infected cattle meat that had bovine spongiform encephalopathy or Mad Cow disease and there are no treatments.

Scientist at University of Texas Health Science Center (Houston, TX, USA) and an international team analyzed urine samples from 68 patients with sporadic Creutzfeldt-Jakob disease, 14 patients with variant Creutzfeldt-Jakob disease, four patients with genetic prion diseases, 50 patients with other neurodegenerative diseases, 50 patients with nondegenerative neurologic diseases and 52 healthy persons.

The investigators used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of misfolded prion protein PrPSc, enabling highly sensitive detection of the protein. 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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University of Texas Health Science Center
Qsonica