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Bridging Interventional Development Gaps

Development of P-321 for Chronic Dry Eye

Dry eye is one of the most frequently diagnosed diseases of the eye, affecting more than 5 million people in the United States. The condition can cause redness, irritation and vision problems. Only a few treatments currently exist for the condition, and they only provide temporary or partial relief. The epithelial sodium channel is a protein found on the surface of many tissues in the body, including the eye. This protein controls hydration by controlling the levels of salt and water absorbed by the surface of the eye. The investigators have developed a drug that inhibits the action of the epithelial sodium channel, preventing salt and water from being absorbed and keeping the eye surface hydrated. This project’s aim is to further develop this drug to prepare it for testing in human clinical trials.

Scientific Synopsis

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-321, produced a concentration-dependent increase in tear output that persists with a long duration of action in normal mice and rats. Furthermore, P-321 significantly increases tear output and improves corneal staining in dry eye models. Taken together, these data suggest that ENaC inhibitors are excellent candidates for clinical development.

Lead Collaborator

Parion Sciences, Durham, North Carolina
Karl Donn, Ph.D.

Public Health Impact

Keratoconjunctivitis sicca, or chronic dry eye disease, 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 may provide long-acting relief from dry eye symptoms.

Outcomes

Work on this project is complete. The investigators successfully filed an Investigational New Drug (IND) application using BrIDGs data and initiated clinical testing.

Project Details

  • Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies
  • ND-directed toxicology

Related Information

News Brief: NEI Sets Stage for New Clinical Trial to Tackle Dry Eye

ClinicalTrials.gov Listing: Study of the Safety and Tolerability of P 321 Ophthalmic Solution in Subjects With Dry Eye Disease

Last updated: 07-25-2017
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