Aquilus Pharmaceuticals, Inc. proposes to evaluate the effects of a proprietary matrix metalloproteinase (MMP) inhibitor, AQU-010, for blocking neuropathic pain and morphine tolerance in a thermal injury (TI) rat model. The goals for Phase I are to scale-up the synthesis of AQU-010, determine its oral pharmacokinetics (PK) and target tissue penetration and then determine its efficacy in the TI-rat model of mechanical and thermal allodynia. A follow-up biomarker and gelatin zymography analysis will be performed to determine if any behavior changes observed from the animal model correspond to changes in metalloproteinase and/or cytokine levels. The ultimate goal of the proposed work is to evaluate whether a matrix metalloproteinase inhibitor can be used to treat pain and/or morphine tolerance in patients suffering from burn injuries without producing euphoria and addiction.
An estimated 1.25 million individuals sustain a burn injury each year of which 50,000-70,000 requiring hospitalization. Morphine remains the gold standard for the management of burn 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 a burn injury. Aquilus will test this inhibitor in a thermal injury animal pain mode to determine if it can block pain without producing tolerance or addiction. If the project is successful, Aquilus Pharmaceuticals will be able to rapidly bring to the clinic a first in class drg that cannot only block pain associated with a burn injury but also halt hyperalgesia and tolerance without producing the side-effects of addiction and withdrawal.