College of American Pathologists
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Looking for CJD: as easy as 14-3-3

March 2001
Mark Uehling

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For pathologists looking to confirm CJD, there is one internationally accepted test that works-and more under development. Specialty Laboratories, of Santa Monica, Calif., offers a $224 test for a neurological protein dubbed 14-3-3, after the chemical formula for one of its seven distinct isoforms and two phosphorylated forms. The test offers 99 percent specificity and 96 percent sensitivity.

Importantly, the 14-3-3 test does not require a biopsy or autopsy of the brain or tonsil, another accepted avenue to a diagnosis of CJD. The Specialty test can be applied to cerebrospinal fluid. "The good thing about it is that the protein is present in the early stages of the disease," says Meeta Patnaik, MD, director of research at Specialty Laboratories.

"If there is a patient with dementia and nonspecific neurologic symptoms, altered mind state," says Dr. Patnaik, "then you do a lumbar puncture and do a test for this particular brain protein. If it’s positive, it strongly supports CJD."

Neurologist Dr. Paul Brown, of the National Institutes of Health, agrees. "It’s a fantastically good test," he says. "It’s better than a Wasserman. It’s so good it’s been included as a solid criterion for the premortem diagnosis of CJD."

At Case Western, neuropathologist Dr. Pierluigi Gambetti concurs. He says the test is especially significant if combined with an EEG. "Then the combination of the two is really extremely supportive. It’s useful, very useful." But Dr. Gambetti notes that the 14-3-3 protein coincidentally will not necessarily remain the gold standard if nvCJD, the disease caused by contaminated beef, ever appears in the United States. "[Using the test] is not that simple; it has to be used with a lot of common sense and care."

A variety of other companies are looking to test blood to find the rogue prions at the root of nvCJD. Dr. Stanley Prusiner, who began writing about transmissible spongiform encephalopathies decades before the outbreak of BSE—and coined the term "prion"—is starting a company to develop a test that looks for the rogue protein.

As Dr. Stephen DeArmond, Dr. Prusiner’s longtime collaborator, explains, that startup company hopes to sell a test that detects various forms of scrapie and the vexing prion itself. "His test looks at both protease-resistant and protease-sensitive scrapie. He has an assay that can distinguish those and that can distinguish both forms of prion protein scrapie from the normal prion protein."

Dr. DeArmond says that if the bureaucratic and corporate obstacles of starting up a company within the University of California system can be overcome, Dr. Prusiner’s test could be marketed this year. Speed could turn out to be important. Several other companies are trying to develop similar tests.

Paradigm Genetics, for example, is developing a blood test for nvCJD using the same monoclonal mouse antibodies used by Prionics, a Swiss company that has pioneered BSE testing in Europe. Other entrants in the field include Idexx Laboratories, of Massachusetts, and Caprion, of Canada. The diagnostic hunt for prions, clearly, is just getting started.