Nonpeptide Somatostatin Agonists for Retinopathy

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR), the leading cause of adult blindness in the United States, is characterized by aberrant neovascularization ultimately leading to blindness. Similarly, choroidal neovascularization is seen in age-related macular degeneration (ARMD), which is the leading cause of blindness in the elderly. Currently, there is no drug treatment for either DR or ARMD patients, with panretinal laser coagulation surgery as the only option to delay blindness. Somatostatinergic drugs are growth factor inhibitors that offer the potential to treat a probable cause of diabetic retinopathy by blocking key mediating steps in disease progression. Clinical trials with somatostatin peptide drugs in DR patients indicate that somatostatinergic drug therapy can stop neovascularization and improve visual acuity. However, the clinical results have been highly variable and have been best for patients receiving high dosage regimens or continuous parenteral treatment. These results are consistent with an inadequate blood-retinal barrier (BRB) penetration of somatostatin peptide drugs to reach target retinal tissues. New non-peptide lipophilic somatostatin receptor agonists described herein have the potential to effectively penetrate the BRB. Using pharmacological in vitro testing (Phase I and II) and animal models of retinal and choroidal neovascularization (Phase II) this study aims to establish structure activity relationships for this innovative class of compounds. The final goal is to identify a small potent somatostatinergic molecule that readily accesses target retinal tissue for clinical testing in DR and ARMD patients.