Abstract

The pathological isoform of the prion protein (PrPres) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. During FY2011, we 1) developed a new prion assay (called eQuIC) that allows for the ultrasensitive and rapid of prions in inhibitor-laden biological fluids such as blood plasma;2) adapted eQuIC to the detection of human, sheep, hamster and mouse prions in blood plasma samples;3) trained and collaborated with human TSE surveillance groups to evaluate the utility of our previously developed RT-QuIC assay for the diagnosis of human sporadic Creutzfeldt-Jakob disease;the data showed that when applied to clinical cerebral spinal fluid samples, RT-QuIC has better sensitivity and specificity than any prior diagnostic test.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001086-03
Application #
8336296
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2011
Total Cost
$976,129
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Haley, Nicholas J; Richt, Jürgen A; Davenport, Kristen A et al. (2018) Design, implementation, and interpretation of amplification studies for prion detection. Prion 12:73-82
Groveman, Bradley R; Orrù, Christina D; Hughson, Andrew G et al. (2018) Rapid and ultra-sensitive quantitation of disease-associated ?-synuclein seeds in brain and cerebrospinal fluid by ?Syn RT-QuIC. Acta Neuropathol Commun 6:7
Orrú, Christina D; Yuan, Jue; Appleby, Brian S et al. (2017) Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease. Sci Transl Med 9:
Saijo, Eri; Ghetti, Bernardino; Zanusso, Gianluigi et al. (2017) Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid. Acta Neuropathol 133:751-765
Foutz, Aaron; Appleby, Brian S; Hamlin, Clive et al. (2017) Diagnostic and prognostic value of human prion detection in cerebrospinal fluid. Ann Neurol 81:79-92
Orrù, Christina D; Groveman, Bradley R; Hughson, Andrew G et al. (2017) RT-QuIC Assays for Prion Disease Detection and Diagnostics. Methods Mol Biol 1658:185-203
Groveman, Bradley R; Orrú, Christina D; Hughson, Andrew G et al. (2017) Extended and direct evaluation of RT-QuIC assays for Creutzfeldt-Jakob disease diagnosis. Ann Clin Transl Neurol 4:139-144
Bongianni, Matilde; Orrù, Christina; Groveman, Bradley R et al. (2017) Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples. JAMA Neurol 74:155-162
Schmitz, Matthias; Cramm, Maria; Llorens, Franc et al. (2016) The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases. Nat Protoc 11:2233-2242
Haley, Nicholas J; Siepker, Chris; Hoon-Hanks, Laura L et al. (2016) Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion. J Clin Microbiol 54:1117-26

Showing the most recent 10 out of 33 publications