Development of a MMP Inhibitor for Neuropathic Pain



 DESCRIPTION (provided by applicant): Aquilus Pharmaceuticals, Inc. proposes to preclinically develop AQU-118 for the treatment of orofacial and general neuropathic pain via a newly discovered mechanism involving matrix metalloproteinases-2 & 9 (MMP-2, MMP-9). AQU-118 is a non-hydroxamic acid containing, MMP inhibitor that is selective for both MMP-2 and MMP-9 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-118, determine its phamacokinetics & 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 & development (PRD) of the synthetic scale- up of AQU-118 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.