Development of P-301 for Chronic Dry Eye
Dry eye is one of the most frequently diagnosed ocular diseases affecting more than 5 million people in the United States alone. Dry eye is a multi-factorial disease, resulting from a common etiology of insufficient tear film causing ocular surface damage and symptoms of ocular discomfort. The few current therapies available, which include immunosuppressive agents and over-the-counter tear replacements, are not sufficiently efficacious for many users or only provide transient relief from dry eye symptoms. Therefore, the development of novel agents to treat dry eye would be of tremendous benefit. The volume of tear film on the ocular surface represents a balance between tear fluid output versus fluid loss via drainage, evaporation or epithelial absorption. Similar to other epithelial tissues, the epithelium of the conjunctiva and cornea are capable of regulating the hydration status of the mucosal surface through active salt and water transport. The epithelial sodium channel (ENaC) regulates sodium (and water) absorption in numerous tissues, including the eye. The inhibition of ENaC in the eye is predicted to preserve lacrimal secretions and maintain hydration on the ocular surface. Parion Sciences has developed a novel series of compounds that specifically and potently inhibit ENaC, which are predicted to be good candidate molecules for clinical development for the treatment of dry eye. In a series of proof-of-concept studies, Parion's lead compound, P-301, produced a concentration-dependent increase in tear output that persists with a long duration of action in normal mice and rats. Furthermore, P-301 significantly increases tear output and improves corneal staining in a dry eye models. Taken together, these data suggest that ENaC inhibitors are excellent candidates for clinical development.
Karl Donn, Ph.D.
Public Health Impact
Keratoconjunctivitis sicca (KCS) or chronic dry eye disease (DED) is one of the most frequently diagnosed ocular diseases, resulting in painful irritation, inflammation on the ocular surface and impaired vision. Parion Sciences is developing a novel therapeutic agent that is predicted to provide long acting relief from dry eye symptoms.
Approved studies are ongoing.
- PK/ADME studies
- IND-directed toxicology