Development of a MMP Inhibitor for Neuropathic Pain

DESCRIPTION provided by applicant Aquilus Pharmaceuticals Inc proposes to preclinically develop AQU for the treatment of orofacial and general neuropathic pain via a newly discovered mechanism involving matrix metalloproteinases andamp MMP MMP AQU is a non hydroxamic acid containing MMP inhibitor that is selective for both MMP and MMP and has been shown to block mechanical allodynia in both the spinal nerve ligation SNL and the chronic constriction injury of the infraorbital nerve CCI IoN rodent models of neuropathic pain The goals for Phase II are to scale up the synthesis of AQU determine its phamacokinetics andamp phamacodynamics PK PD in the SNL rat model and complete in vitro safety studies within the first year Year two will entail the process research andamp development PRD of the synthetic scale up of AQU culminating in its GMP manufacture as well completing various pivotol GLP animal toxicity studies The ultimate goal of the proposed work is to rapidly develop a safe and effective drug for the treatment of chronic orofacial and general neuropathic pain that produces no addictive or euphoric side effects PUBLIC HEALTH RELEVANCE Millions of Americans suffer from chronic neuropathic pain for which no current single drug treatment is effective in more than of patients Of those drugs that are effective their side effect profile and or propensity for addiction make them poor candidates for long term use Aquilus Pharmaceuticals plans to develop a compound that has been found to block neuropathic pain in various animal models via a newly discovered pain pathway The purpose of the proposed work is to further study this new compound and determine whether it is safe enough and can be made in sufficient quantities to be tested in humans If the project is successful Aquilus Pharmaceuticals will be able to bring to the clinic a pain drug with a novel mechanism of action that would be focused on the treatment of chronic orofacial and general neuropathic pain without producing any addictive or euphoric side effects