Abstract
INTRODUCTION: Current treatments for Glioblastoma (GBM) are inadequate and immunotherapeutics may provide better outcomes for patients. Human recombinant Decorin is a glycoprotein that modulates inflammation & GBM growth by inhibiting Transforming Growth Factor, Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor. As Decorin is found in human tissue rich in fibrillar collagen (e.g. skin, heart, bone lung & liver) it is a potentially safe drug to be trialled in humans. METHOD: The local immune and microglial response to intracerebral injections of Decorin was investigated. Rats (n = 6 for each group) received either an injection of PBS (control) or 5¼l 5mg/ml Decorin and were sacrificed at 30min, 3 & 24 hrs or after continuous infusion of either PBS (control) or Decorin for 7 days. CSF samples were taken and analysed by ELISA and Luminex for presence of Decorin and change in inflammatory markers. Immunohistochemistry was also performed to investigate the effects of Decorin on microglia using OX42. RESULTS: There was no inflammatory reaction or cavity formation in brain. Decorin supressed the microglial response after direct injections into the brain compared to PBS control. At 30 mins, low levels of decorin were detected (with ELISA) in CSF and serum but none was detected at 3hrs and 24hrs after injection. CONCLUSION: Decorin showed no dose limiting toxicity, whilst maintaining its immunomodulatory effects in brain. These findings show a safe pharmacokinetic and toxicological profile.
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