Detecting Human Prion Disease
At a Glance
- New tests can rapidly and accurately diagnose Creutzfeldt-Jakob
disease, an incurable and ultimately fatal neurodegenerative disorder.
- Early diagnoses of prion diseases could help prevent their spread and aid in the development of experimental treatments.
Prion diseases originate when, for reasons not fully understood,
normally harmless prion proteins become abnormal, clump together, and
accumulate in the brain. The diseases are characterized by sponge-like
holes in brain tissue. They are notoriously difficult to diagnose,
untreatable, and ultimately fatal.
Sponge-like lesions in the brain tissue of a CJD patient. Image courtesy of CDC.
Human prion diseases include sporadic, familial, and variant
Creutzfeldt-Jakob disease (CJD). Sporadic CJD is the most common,
affecting an estimated 1 person per million worldwide each year.
Sporadic CJD is caused by the spontaneous transformation of normal
prions into abnormal ones. Other prion diseases include scrapie in
sheep and bovine spongiform encephalopathy (BSE), or mad cow disease, in
cattle.
Previously, a definitive CJD diagnosis could only be made by
testing brain tissue after death or by biopsy in living patients. In
the August 7, 2014, issue of the
New England Journal of Medicine,
researchers at NIH’s National Institute of Allergy and Infectious
Diseases (NIAID) and Italian colleagues described a less invasive test.
Dr. Gianluigi Zanusso and scientists at the University of
Verona in Italy developed a way to collect olfactory neurons connected
to the brain. The technique involves inserting a rigid fiber-optic
rhinoscope into the patient’s nasal cavity. A sterile brush is then
inserted alongside the scope. The brush is gently rolled along the
mucosal surface to collect the neurons.
The scientists tested for the presence of prions using a
technique called real-time quaking-induced conversion—or RT-QuIC. Dr.
Byron Caughey’s group at NIAID, with collaborators at Nagasaki
University, had previously developed the method to test cerebrospinal
fluid for the presence of prions.
The researchers tested nasal samples from 31 people with
sporadic CJD, 12 who had other neurologic diseases, and 31 with no
neurologic disorder. The test correctly identified 30 of the 31 CJD
patients (97% sensitivity) and correctly showed negative results for
all 43 of the non-CJD patients (100% specificity). By comparison, tests
using cerebral spinal fluid were 77% sensitive and 100% specific, and
took twice as long to complete.
“This exciting advance, the culmination of decades of studies on
prion diseases, markedly improves on available diagnostic tests for CJD
that are less reliable, more difficult for patients to tolerate, and
require more time to obtain results,” says NIAID Director Dr. Anthony
S. Fauci. “With additional validation, this test has potential for use
in clinical and agricultural settings.”
Another NIH-funded team, led by Dr. Claudio Soto of the
University of Texas Health Science Center at Houston Medical School,
developed a method for detecting prions in urine. They described the
technique, called protein misfolding cyclic amplification, in an
accompanying paper in the same journal. The test detected prions in 13
of 14 urine samples from patients with variant CJD—a type of CJD caused
by exposure to BSE. The test didn’t detect prions in urine samples
from healthy controls or from patients with other neurologic disorders,
including sporadic or familial CJD. These results suggest that prions
in urine are an exclusive feature of variant CJD.
The researchers will continue to develop and assess these tests in patients with CJD and other prion diseases.
