Didox‐A Multipotent Drug for Treating Demyelinating disease

Abstract

Chronic experimental allergic encephalomyelitis (EAE) is an animal model for multiple sclerosis the most common demyelinating disease. Didox is a polyhydroxyphenol which can inhibit biological activities important for the progression of EAE. After induction of chronic EAE, didox was given daily to C57Bl/6 mice either by intraperitoneal injection (275 mg/kg) or by oral gavage (550 mg/kg in carboxymethylcellulose); mice were evaluated daily for clinical severity (stage 4=maximum severity). Didox given prior to the onset of disease, delayed the onset and reduced the severity of disease. Didox given at the peak of disease completed reversed clinical symptoms. Didox given one week after peak disease reduced clinical symptoms from 4 to 2. In a dose dependent manner didox inhibited peripheral T‐cell proliferation, secretion of both IFN‐gamma and Il‐17a by activated T‐cells and secretion of nitrite by microglia. Morphological examination of the CNS of didox‐treated mice which had reversed from stage 4 to stage 0 revealed preservation of axons and myelin similar to what was observed in the CNS of mice when they initially reached stage 4. EM analysis of didox treated animals revealed lymphocytes trapped in the perivascular space. The pleotrophic effects of didox make it an ideal candidate for demyelinating disease therapy. (Supported by the Dept. Veterans Affairs and Molecules for Health, Richmond, VA.)