The MediciNova Approach
MN-001 is a novel, orally bioavailable compound under development for the treatment of bronchial asthma. MN-001 combines the positive attributes of the leukotriene (LT) antagonists and inhaled steroids while maintaining an acceptable clinical safety profile. In vitro receptor binding and enzyme inhibition assays have identified several mechanisms by which MN-001 may produce its anti-asthma activity in preclinical models, including LT receptor antagonism and inhibition of phosphodiesterases III and IV, 5-lipoxygenase, phospholipase C and thromboxane A2. Preclinical animal pharmacology studies have demonstrated that MN-001 inhibits the airway hyper-reactivity that causes bronchoconstriction through a reduction of airway inflammation. In addition, MN-001 was shown to be well tolerated in extensive rodent and dog toxicology testing.
The diagram above shows the asthma cascade. Mast cells can be stimulated to release pro-inflammatory chemical mediators by either extrinsic/allergic or intrinsic (e.g., cold, exercise) triggers. MN-001 has been shown to block these chemical mediators and inhibit eosinophil infiltration, and therefore inhibit acute bronchoconstriction and chronic inflammation in the lung as illustrated above. Thus, MN-001 has the potential to alleviate acute asthmatic symptoms and to block late phase inflammation.