The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing-- Remitting Multiple Sclerosis Mouse Model

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellularsignaling molecule. A direct correlation between increased amount of S100B and demyelination andinflammatory processes has been demonstrated. The aim of this study is to investigate the possiblerole of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of diseaseprogression in the relapsing-remitting experimental autoimmune encephalomyelitis mouse modelof multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecularanalysis performed in the central nervous system, we observed that pentamidine is able to delay theacute phase of the disease and to inhibit remission, resulting in an amelioration of clinical scorewhen compared with untreated relapsing-remitting experimental autoimmune encephalomyelitismice. Moreover, we observed a significant reduction of proinflammatory cytokines expressionlevels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxidesynthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modifythe neuropathology of the disease, reducing immune infiltrates and partially protecting the brainfrom the damage. Overall, our results indicate that pentamidine targeting the S100B protein is anovel potential drug to be considered for multiple sclerosis treatment.