. Aquilus Pharmaceuticals, Inc. proposes to evaluate the effects of a selective, dual active, matrix metalloproteinase-2 (MMP-2) and MMP-9 inhibitor, AQU-118, in the superoxide dismutase-1 (SOD-1) mouse model of amyotrophic lateral sclerosis (ALS). The goals for Phase I are to chemically synthesize AQU-118, determine its oral pharmacokinetics (PK) in SOD-1 mice and then determine its efficacy in the SOD-1 mouse model of ALS with dose response. Lastly, a tissue morphology & immunohistochemical study will then be performed to determine whether or not oral dosing with AQU-118 results in any biochemical changes within spinal tissues as compared to controls. The ultimate goal of the proposed work is to evaluate whether a dual active MMP-2/-9 inhibitor can be used to treat ALS.
. Over 5000 people are diagnosed in the US with amyotrophic lateral sclerosis (ALS) or Lou Gehrig?s Disease each year. The life expectancy for those diagnosed with ALS on average is two to five years. The primary FDA approved drug, Riluzole, has been found to extend the life of people with ALS (PALS) by only a few months. Aquilus Pharmaceuticals (Aquilus) will test a novel inhibitor of a group of proteins that have recently been found to be upregulated in both PALS and in a key mouse model of the disease. Aquilus will test this inhibitor in this ALS mouse model to determine if it can not only slow or arrest the disease but more importantly prolong overall survival. If the project is successful, Aquilus will be able to rapidly bring to the clinic this first in class experimental drug to treat this devastating disease.
