Orally active MMP inhibitor for the treatment of bone cancer pain

DESCRIPTION provided by applicant Aquilus Pharmaceuticals Inc proposes to evaluate the effects of a proprietary matrix metalloproteinase MMP inhibitor AQU for blocking mechanical allodynia and bone andamp nerve compression pain in a rodent model of bone cancer The goals for Phase I are to scale up the synthesis of AQU determine its oral pharmacokinetics PK and target tissue penetration and determine its efficacy in a mouse bone cancer pain model via NCTC fibrosarcoma cell implantation The primary read outs will be measuring mechanical allodynia and motion induced pain The secondary read out will be to measure the extent of bone density loss and tumor growth A follow up biomarker and gelatin zymography analysis will be performed to determine if any behavioral changes observed from the animal model as a result of dosing with AQU correspond to changes in metalloproteinase MMP MMP cytokine IL IL andamp EphB EphrinB levels in serum and or target tissue The ultimate goal of the proposed work is to evaluate whether a matrix metalloproteinase inhibitor can be used to significantly reduce bone cancer pain and bone density loss without the side effects of euphoria tolerance and addiction PUBLIC HEALTH RELEVANCE Over people in the US are diagnosed with bone cancer a majority of which will suffer severe pain as a consequence Morphine remains the gold standard for the management of bone cancer pain despite having the significant side effects of tolerance hyperalgesia and addiction Aquilus Pharmaceuticals will test a novel inhibitor of a group of proteins that have recently been discovered to be involved in the initial inflammatory cascade resulting from bone cancer and neuropathic pain A primary objective for Aquilus will be determine if this inhibitor can block pain in a rodent bone cancer pain model when given orally A secondary objective will be to see if this inhibitor can reduce the rate of bone density loss due to cancer If the project is successful Aquilus Pharmaceuticals will be able to rapidly bring to the clinic a first in class drug that can block pain and bone loss associated with bone cancer