Adiponectin is a protective adipokine that counterbalances the negative effects of obesity and metabolic malfunctions, mostly through anti-inflammatory effects. The designer adiponectin receptor agonist peptidomimetic ADP355 exhibits clinically promising systemic efficacies in mouse models of scleroderma, lipodystrophy, breast cancer, liver injuries and atherosclerosis. Perhaps the fastest route to the clinics is topical administration against dry eye disease.
In a mouse model mimicking human conditions, adiponectin protein effectively and significantly reduces the signs of dry eye (demonstrating increased tear production and reduced corneal damage) and decreases the expression of pro-inflammatory cytokines. Since the full length protein is not amenable for pharmaceutical development, we focused on ADP355 as a preclinical drug candidate. Indeed, in the mouse model of dry eye disease, ADP355 was as effective as adiponectin protein in improving disease measures including: reducing corneal damage, improving tear film stability and volume, and reducing the inflammatory response. Thus, ADP355 improved all components of dry eye disease: ocular surface disease, ocular surface inflammation and epithelial cell damage.
As an eye drop formulation, ADP355 is most soluble and stable at low pH in acetate buffer. Aggregation, a typical feature of adiponectin protein was observed for the peptide as well, albeit at a manageable level and not interfering with reaching a therapeutic composition. If approved, ADP355 would be an important addition to the armamentarium in the treatment of dry eye disease (a multi-billion dollar market) that would greatly benefit from new therapeutics with long-lasting and robust efficacies.