Experimental non-invasive tests detect rare brain disease

By Gene Emery NEW YORK (Reuters Health) - An analysis of two experimental tests for Creutzfeldt-Jakob disease shows that cells in the nose or a urine sample can detect versions of the brain-destroying illness. The urine test proved effective at identifying the human form of mad cow disease. The research, reported in the New England Journal of Medicine, may make it far easier to diagnose the illness, track its progress in the body and evaluate potential treatments. "That would help us in our diagnosis, and we wouldn't have to do invasive procedures. So we're now moving less and less into the invasive procedure business, and that's great," said Dr. Beau Ances of the Washington University School of Medicine in St. Louis, who was not connected with either study. Creutzfeldt-Jakob disease has long been considered rare, affecting only about one in a million people, with 85 percent of the cases arising sporadically and the remaining 15 percent running in families. But there are hotspots, such as the variant that loomed as a threat in England several years ago as a result of contaminated beef. Perhaps 1 in 2,000 people in the United Kingdom may be carriers but it's not clear if they will ever fall ill. The disease is caused by a misfolded protein, called a prion, that has the unique ability to distort the shapes of otherwise healthy versions of the same protein, spreading the infection in the body and doing most of its damage in the brain. The way the prion misfolds determines the characteristics of the disease. Symptoms may differ but, in the end, it makes brain tissue develop holes like a sponge, eventually causing death. There is no accepted treatment. Diagnosis is difficult because it can show up in so many ways - including balance problems, memory loss, depression or paranoia - depending on which part of the brain is sustaining the most damage. A definitive diagnosis comes from taking a sample of brain tissue. When that's done, the instruments must be discarded out of fear that they might be contaminated by the prions responsible for the illness. That's why doctors are desperately looking for a safer alternative. Doctors can also look for evidence of the disease using an MRI scan or look for signs of the prions in spinal fluid, another invasive test. In one of the tests described in the new studies, tissue was collected from the top of the nasal cavity by brushing it with a swab. When the tissue was processed, doctors correctly identified 30 out of 31 cases of sporadic or inherited Creutzfeldt-Jakob. In contrast, conventional testing with cerebrospinal fluid only catches 77 percent of cases. The nasal-tissue test also correctly identified all 43 cases where the person did not have the disease. The test was not fooled by people with Alzheimer's disease and other brain-related problems that involve deformed proteins. "It should make Creutzfeldt-Jakob disease diagnosis - which has been a real problem - easier, faster and more definitive," coauthor Dr. Byron Caughey of the National Institute of Allergy and Infectious Diseases told Reuters Health by phone. "That in itself is a very important thing." "It may provide a relatively non-invasive way to follow disease progression," he added. The test used in the study took about two and a half days to complete, "but we can do it a lot faster now - within a day," Caughey said. He noted that the implications may extend beyond Creutzfeldt-Jakob disease. Already, he said, people who work other neurodegenerative diseases that involve protein misfolding, such as Alzheimer's, are looking for telltale signs from tissue collected from the upper nasal cavity, where the nerve cells are very close to the brain. The urine test only worked for people who had the variation of Creutzfeldt-Jakob that is the human equivalent of mad cow disease, acquired by eating contaminated cattle meat. It detected cases with 93 percent accuracy and the test came up negative in all 224 people who were healthy or had other neurologic diseases such as Alzheimer's, Parkinson's and sporadic or inherited Creutzfeldt-Jakob. The urine test, which takes about four or five days to process, appears to work even for samples taken 117 days apart, suggesting there may be a broad window in which to test. "It could be useful for assessing individuals in high-risk areas," Ances said. Coauthor Dr. Claudio Soto of the University of Texas Medical School at Houston told Reuters Health that he was "surprised it worked so well because the amount of prion in urine is very tiny." He said there's a good reason why it didn't work with other types of Creutzfeldt-Jakob. "These are completely different diseases, actually" because the prions involved with the mad cow form enter the body by eating and get into the blood, replicating in organs besides the brain, he said. "There's much more involvement of peripheral organs in the body" so telltale signs in the urine are much more likely than in other forms of the illness. Neither test is commercially available but laboratories would have the ability to do them, the researchers from both groups said. Soto said he is hoping to eventually market the urine test, which is patented. SOURCE: http://bit.ly/1s3acro and http://bit.ly/1p3ph9U New England Journal of Medicine, online August 6, 2014.