Early diagnosis of multiple sclerosis
Santarpia, Concetta (2009) Early diagnosis of multiple sclerosis. [Tesi di dottorato] (Inedito)
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Multiple sclerosis (MS) is characterized by a chronic inflammation, demyelination and gliosis resulting in damage of the central nervous system (CNS). No definitive diagnostic tests for multiple sclerosis is currently available. Using the CSF from MS patients on cultures of differentiating oligodendrocytes (MO3.13), we have found that the expression of a specific Marker (Marker C) is significantly reduced compared with control groups. Marker-C is a stress marker. We do not disclose the identity of Marker-C because it is under patentin process as a marker of early multiple sclerosis. Moreover, we have found in CSF from MS patients molecules that act on redox pathways and interfere with hydrogen peroxide induced oligodendrocyte maturation. In differentiated MO3.13 cells, treated with CSF from MS patients, there is also, a significant increase of other 2 markers (Marker-A and Marker-B), which are negative differentiation markers, compared to cells treated with CSF from control group. These results indicate that CSF from MS patients contain specific molecule(s) that inhibit the oligodendrocyte differentiation by increasing the expression of the Marker-A and -B. Combining the variation of the stress marker, Marker-C, with the negative differentiation markers, Marker-A and -B, we have developed a mathematical MS index (AxB/C). We estimate that the test can detect a MS patient with a +/-5% error (false negatives). The identification of specific markers of oxidative stress and/or negative differentiation (markers A, B and C) modulated in M03.13 cells after MS CSF stimulation, may represent an indirect measurement of a specific cell receptor activation. This assay can be used as guide to develop a new diagnostic method for an early diagnosis of MS. Our test provides an opportunity to measure at an early stagethe activation of a specific signal transduction pathway resulting in the block of differentiation of oligodendrocytes. We conclude that in the cerebrospinal fluid (CSF)derived from patients with multiple sclerosis there is a molecule(s) that acts on oxidative stress pathways and that inhibits oligodendrocyte differentiation, altering the normal re-myelinization process.
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