#2020016 - Inhibition of Thrombin for Treatment of Retinal Pathologies
Joab Chapman, Efrat Shavit-Stein, Ygal Rotenstreich, Yifat Sher
| Categories | Therapeutics & Compositions |
| Patent Status | Pending |
Development Stage- The safety and acute toxicity of the molecule was demonstrated in mice. Neither bleeding nor death were observed following the administration of 50 and 100 times doses that were tested. Coagulation tests were conducted on human plasma and found no clinical significant effects on PTT, PT and thrombin time in 10 and 100 folds of the concentration applied for treatment in mice.
Background and Need
Diabetic retinopathy (DR), a major complication of diabetes mellitus, is one of the leading causes of sight-loss among the working age population of industrialized regions.1 In 2010 it was estimated that DR affected over 100 million patients worldwide and these estimates are expected to rise to over 190 million by 2030 Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the major sight-threatening complications of diabetes.
Retinal degeneration diseases including age related macular degeneration (AMD) and retinitis pigmentosa (RP) are a leading cause of blindness worldwide. AMD affects mostly people age 65 and up. With the aging of the population, the prevalence of AMD is predicted to increase sharply reaching 288 million in 2040. Retinitis pigmentosa (RP) is a group of incurable hereditary retinal degeneration diseases that affects nearly 2 million patients worldwide and is characterized by progressive degeneration of rod and cone photoreceptors.
The inventors have collected many significant findings supporting the role of PAR-1 activation in mediating neurological dysfunction in diabetes. These findings suggest that the PAR-1/ /thrombin signaling axis may present a new avenue for therapeutic intervention for diabetic retinopathy, potentially targeting the pathological angiogenic and neurodegeneration processes.
Invention
A breakthrough treatment for ameliorating retinal photoreceptor degeneration based on eye drops and systemic medication that include inhibitors of the PAR-1 pathway. This treatment is predicted to slow down or even prevent vision loss in patients with retinal degeneration including DR, RP and AMD patients. The inventors have developed novel and unique molecules that specifically block the interaction of thrombin and PAR-1, based on the specific thrombin-recognition site in PAR-1 (the sequence PESKATNATLDPR).
