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A protein fragment called 12.5 kda cystatin may generate first simple test for multiple sclerosis

Johns Hopkins scientists report the discovery of a protein found only in cerebrospinal fluid that they say might be useful in identifying a subgroup of patients with multiple sclerosis (MS) or identifying those at risk for the debilitating autoimmune disorder.

MS strikes over 10,000 Americans each year, most of whom are women, and causes weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. It is a disorder in which the immune system destroys myelin, the covering of nerves that helps transmit signals. Cerebrospinal fluid (CSF) is the watery fluid that surrounds and cushions the brain and spinal cord.

The federally funded Hopkins research, reported in the February issue of the Annals of Neurology, is important, the researchers say, because unlike other autoimmune diseases in which the body attacks its own tissues, MS cannot be diagnosed with a simple blood or other test.

While it is recognized that there might be several forms of MS, laboratory-based tests need to be developed to diagnose these subtypes.

"There is the possibility now that the protein we identified, 12.5 kDa cystatin, can be used to diagnose MS, perhaps in its earliest stages, and also to monitor treatment by measuring its levels in CSF," says Avindra Nath, M.D., a professor in the Department of Neurology at The Johns Hopkins University School of Medicine and lead author of the study.

Working with human CSF, the Hopkins team showed that 12.5 kDa cystatin is a breakdown product of a larger protein called cystatin C or 13.4kDa, which in turn blocks activity of some enzymes, including cathepsin B. Cathepsin B has been linked to demyelination-the destruction of the nerve sheath. The term kDa refers to Kilodalton, the weight of one molecule of a substance.

"In fact, those patients who had more of the breakdown product of 12.5 kDa cystatin also seemed to have the highest cathepsin B inhibition," Na
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Contact: Eric Vohr
evohr1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
3-Mar-2006


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