Effectiveness of VBP15, a dissociative steroidal analogue, on chronic inflammation in a mouse model of multiple sclerosis

DESCRIPTION provided by applicant Glucocorticoids GCandapos s such as prednisolone are used frequently to induce remission and treat multiple sclerosis MS Despite effectiveness many GC mediated detrimental side effects including osteoporosis and muscle atrophy limit long term chronic treatment of MS patients These side effects are believed to be mediated by well described glucocorticoid response element GRE mediated transcriptional properties transactivation whereas efficacy is mediated by trans repression of NFkB pro inflammatory pathways ReveraGen BioPharma has identified a lead compound VBP that is a novel dissociative steroid designed to maintain the anti inflammatory efficacy of traditional steroids through NFkB inhibition and GR translocation yet has lost GRE mediated transcriptional activities leading to much less side effects typically associated with traditional glucocorticoid drugs no osteopenia growth stunting or steroid myopathy Importantly VBP has been shown to reduce inflammatory activity in vivo across multiple murine models of disease Furthermore we have demonstrated in a pilot study that VBP significantly reduces the severity of disease in the experimental autoimmune encephalomyelitis EAE model of multiple sclerosis preliminary data Thus VBP may represent a safer and more effective alternative to traditional glucocorticoids in the treatment of MS The goal of this STTR research is to extend preclinical evaluation of VBP by assessing the effect of treatment on disease in the mouse chronic relapsing remitting EAE model using published recommendations for pre clinical studies We hypothesize that VBP treatment after disease onset will result in similar anti inflammatory activity compared to prednisolone but possess a much reduced side effect profile As VBP has already entered Phase clinical trials in adult healthy volunteers transition to MS trials would likely ensure shortly after the successful completion of the proposed STTR grant PUBLIC HEALTH RELEVANCE The goal of this STTR research is to extend preclinical evaluation of VBP with a blinded study of efficacy endpoints in the relapsing remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis using published recommendations for pre clinical studies VBP may represent a safer and more effective alternative to traditional glucocorticoids in the treatment of multiple sclerosis