An Improved Test for Creutzfeldt-Jakob Disease

Byron Caughey, PhD Senior Investigator Rocky Mountain Laboratories National Institute for Allergy and Infectious Diseases National Institutes of Health Hamilton, Montana 59840MedicalResearch.com Interview with:
Byron Caughey, PhD
Senior Investigator
Rocky Mountain Laboratories
National Institute for Allergy and Infectious Diseases
National Institutes of Health
Hamilton, Montana 59840

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Caughey: One of the challenges in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases such as Creutzfeldt-Jakob disease (CJD) because the causative prion agents are deadly, transmissible and unusually resistant to decontamination. A recently developed test called Real-Time Quaking-Induced Conversion (RT-QuIC) allows for highly sensitive and specific detection of Creutzfeldt-Jakob disease using human cerebrospinal fluid (CSF) or nasal brushings and is being widely implemented as a key diagnostic tool. However, the currently implemented CSF-based test takes 2.5-5 days and misses 11-23% of Creutzfeldt-Jakob disease cases. We have now markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced analytical and diagnostic sensitivity. Analysis of 11 Creutzfeldt-Jakob disease patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples sporadic Creutzfeldt-Jakob disease patients were positive while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Caughey: Our improved RT-QuIC assay should allow for much faster, more accurate and practical testing for Creutzfeldt-Jakob disease using patients’ CSF samples.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Caughey: Future studies should be aimed at further evaluating the diagnostic utility of the RT-QuIC test using much larger numbers of CSF specimens and additional diagnostic centers. In a larger sense, the RT-QuIC assay provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer’s, Parkinson’s and tauopathies.

Citation:

Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid.

Orrú CD, Groveman BR, Hughson AG, Zanusso G, Coulthart MB, Caughey B.

mBio. 2015 Jan 20;6(1). pii: e02451-14. doi: 10.1128/mBio.02451-14.

MedicalResearch.com Interview with:, Byron Caughey, PhD, Senior Investigator, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, & Hamilton, Montana 59840 (2015). An Improved Test for Creutzfeldt-Jakob Disease MedicalResearch.com