Effectiveness of VBP15, a dissociative steroidal analogue, on inflammation in a mouse model of arthritis

DESCRIPTION provided by applicant Glucocorticoids GCandapos s such as prednisolone are used frequently to induce remission and treat rheumatoid arthritis RA Despite effectiveness many GC mediated detrimental side effects including osteoporosis and muscle atrophy limit long term chronic treatment of RA patients In addition juvenile arthritis patients suffer from th side effect of significant stunting of linear growth These side effects are believed to be mediated by well described glucocorticoid response element GRE mediated transcriptional properties transactivation whereas efficacy is mediated by transrepression 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 collagen antibody induced mouse model of arthritis preliminary data Thus VBP may represent a safer and more effective alternative to traditional glucocorticoids in the treatment of RA where treatment of elderly RA patients may show efficacy with loss of osteopenia and steroid myopathy side effects and loss of growth stunting side effects important in juvenile RA The goal of this STTR research is to extend preclinical evaluation of VBP with a blinded study of efficacy endpoints in a chronic collagen induced mouse model of arthritis CIA 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 RA 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 a chronic collagen induced mouse model of arthritis using published recommendations for pre clinical studies VBP may represent a safer and more effective alternative to traditional glucocorticoids in the treatment of
rheumatoid arthritis