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Wednesday, August 13, 2014

Misfolded Prion Proteins Found in the Urine of Patients with Variant Creutzfeldt-Jakob Disease

by Rebecca Hiscott


Researchers report in a new study that they have detected infectious prions in the urine of patients with variant Creutzfeldt-Jakob disease – a fatal degenerative illness that has been linked with the consumption of beef contaminated with bovine spongiform encephalopathy (BSE) or “mad cow disease.”


Misfolded prion proteins, or PrPSc, are believed to cause BSE and other transmissible spongiform encephalopathies, but the diagnosis is usually made on the basis of clinical examination and confirmed in a postmortem analysis of brain tissue.


            Only 228 cases of variant Creutzfeldt-Jakob disease have been reported so far worldwide, according to the Centers for Disease Control and Prevention (CDC); the most recent case in the US was confirmed by autopsy in June.



Magnetic resonance imaging of a patient with variant CJD. From Collie DA. Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. AJNR 2003;24:1560.


The study, published in the August 7 issue of the New England Journal of Medicine, used a protein misfolding cyclic amplification (PMCA) assay, which mimics in vitro the prion replication process that occurs in prion disease. The researchers looked for trace amounts of prions in urine samples from 14 patients with variant Creutzfeldt-Jakob disease, 68 patients with sporadic Creutzfeldt-Jakob disease, 4 patients with genetic prion diseases, 50 patients with other neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, 50 patients with nondegenerative neurologic disorders such as multiple sclerosis and epilepsy, and 52 healthy people.


Misfolded prion proteins were detected in 13 of 14 urine samples of patients with variant Creutzfeldt-Jakob disease with an estimated sensitivity of 93 percent and specificity of 100 percent. The assay did not detect PrPSc in any of the other 224 samples.  The findings indicate that “with this technique, PrPSc is detectable exclusively in the urine of patients with variant Creutzfeldt-Jakob disease,” the authors wrote.


They estimated that the concentration of prion proteins in patients’ urine is approximately 2,000 molecules of prion protein monomer per milliliter of urine, an extremely small amount.


“What could be less invasive than detecting this disease in urine?” lead study author Claudio Soto, PhD, professor of neurology at the University of Texas Health Science Center School of Medicine, said in a news release. “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.”


These findings could potentially be used as a diagnostic tool not just for patients with variant Creutzfeldt-Jakob disease, but for asymptomatic people who may be carriers of the illness as well. A 2013 study published in the British Medical Journal estimated that around one in 2,000 people in the United Kingdom could be carriers of an asymptomatic form of variant Creutzfeldt-Jakob disease, which could potentially infect others via blood transfusions, the authors noted.


            “Further studies are needed to determine whether the detection of PrPSc in urine can be used diagnostically,” they concluded.


Read the latest updates from the CDC on variant CJD here: For more coverage of variant Creutzfeldt-Jakob disease in Neurology Today, browse our archives here: