As it is, the way to confirm the diagnosis of the fatal disease is by direct examination of brain tissue, which requires a brain biopsy, or by autopsy. But two studies in this week’s issue of NEJM report preliminary data for novel ways to detect the abnormally folded prion protein, in urine and nasal brushings of affected patients. They offer hope for non-invasive methods to diagnose both variant Creutzfeld-Jacob Disease (vCJD)– so-called ‘mad cow disease’—and the sporadic form of CJD.
In one study, Christina Orrú and colleagues investigated how accurate an amplification technique called “real-time quaking induced conversion” is to diagnose sporadic CJD in living patients. This technique is an assay that works by causing the diseased prion protein to react with recombinant prion protein to form amyloid, which is detected with a dye. The technique has shown promise for detecting CJD in cerebrospinal fluid samples, with a sensitivity of 80 to 90 percent. At the same time, the abnormal prion protein is known to accumulate in the olfactory epithelium of patients with CJD – leading investigators to question whether that might be an easier-to-reach diagnostic site.
With that background, the authors enrolled 31 patients with rapidly progressive dementia due to definite or probable CJD and 43 patients with other neurodegenerative disorders. The investigators took nasal brushing samples and CSF samples from these patients and found that the sensitivity to detect CJD was 97 percent in nasal brushings, compared to 77 percent in CSF samples. Both tests were highly specific for CJD.
And olfactory mucosa isn’t the only unexpected place to find the misfolded prion proteins, an accompanying paper in this week’s NEJM suggests. Fabio Moda and colleagues took urine samples from 14 patients with variant CJD and more than 200 patients with other neurologic diseases, including the sporadic form of CJD Using a technique that allows amplification of “minute” samples of prion protein, the authors detected abnormal prion proteins in 13 of the 14 variant CJD patients and none of the other patients with other diseases.
Although questions remain — for instance, how accurate will these tests prove to be in making the diagnosis and how early in the disease process can the prion protein be detected — both studies suggest promise for new ways to diagnose both variant and sporadic CJD in affected patient’s olfactory mucosa and urine. These findings could point the way toward further research into a non-invasive way to establish a definitive diagnosis of this devastating disease.
For more on this topic, see the accompanying editorial from the University of Melbourne’s Dr. Colin Masters.