09/25/1996 07:00:00

New Diagnostic Test Announced for Group of Brain Diseases

PASADENA— Scientists have developed a simple diagnostic test for transmissible spongiform encephalopathies (TSEs), a group of invariably fatal brain diseases that include "Mad Cow" disease in cattle and Creutzfeldt-Jakob disease (CJD) and kuru in humans.

According to Dr. Michael Harrington of the California Institute of Technology, he and his colleagues at the National Institute of Neurological Disorders and Stroke have developed the test by identifying a diagnostic protein found in the spinal fluid of infected humans and animals. Their research appears today in the New England Journal of Medicine.

Harrington, a scientist at Caltech's Beckman Institute, says that the test is an important contribution to public health because it can help prevent future transmissions of the diseases. "This should reduce the risk of accidental transmission, allow better patient management, and could even provide an objective measure for any future treatment," Harrington says.

Dr. Kelvin Lee, Harrington's colleague at Caltech, adds that the test should be of considerable interest in Great Britain. In the last year, a form of the disease known as bovine spongiform encephalopathy (also known as BSE, or "Mad Cow" disease) has been linked to a new strain of CJD, which has affected several individuals in Britain.

"This test potentially enables us to screen cattle and herds for BSE and thus reduce the possibility that BSE-contaminated beef could enter the food chain," Lee says. "Moreover, it will provide a means for selectively destroying BSE cattle as opposed to unaffected cattle, and make the international exchange of animals more safe."

TSEs are degenerative diseases of the nervous system characterized by rapidly progressive dementia and uncontrolled limb spasms in both humans and animals. The diseases are always fatal, and postmortem examinations reveal spongelike holes in the brain.

The causitive agent of these transmissible diseases is believed to be a prion, an infectious protein that accumulates in the brain and results in neuronal destruction. Prions have been shown to be particularly resistant to standard decontamination procedures.

Diagnosis of these disorders has relied on brain biopsy or postmortem examination for the presence of the prion. In work published by Harrington in 1986, he showed that a particular protein was present in the cerebrospinal fluid of patients affected with CJD and could serve as a useful molecular marker for this disease.

The new findings identify that protein as 14-3-3, a normal neuronal protein. "We hypothesize that 14-3-3, which is normally present in neurons, leaks into the spinal fluid as a result of the neuronal destruction that occurs in TSEs," says Harrington. The identification of the protein as 14-3-3 has enabled the development of a simpler test for the diseases.

Also involved in the study are Drs. Clarence J. Gibbs, Jr., Kimbra Kenney and Gary Hsich, all of the National Institutes of Health's National Institute of Neurological Disorders and Stroke.

Written by Robert Tindol