Protection and Treatment of the Ocular Surface Barrier

DESCRIPTION provided by applicant Dry eye a group of disorders that affects million people over the age of in the USA today is characterized by inadequate hydration and lubrication of the ocular surface The final common pathway for all types of dry eye is disruption of the ocular surface barrier which can be assessed by quantifying uptake of water soluble dyes applied topically to the ocular surface In preliminary data using a preclinical model it is shown that topical delivery of clusterin CLU a natural homeostatic tear protein prevents and ameliorates barrier disruption in a preclinical model by a remarkable sealing mechanism dependent on attainment of a critical all or none threshold The anti inflammatory proteostatic and cytoprotective activities of CLU are well known It is shown that CLU binds to the ocular surface subjected to desiccating stress selectively and positioned in this way it also protects barrier structure The long term goal of Proteris Biotech Inc is to translate CLU to the clinic a an FDA approved biotherapeutic This Phase I STTR application has two immediate scientific goals to establish and perform good manufacturing practices GMP compatible production of a human recombinant form of CLU called andquot Protearinandquot under non GMP conditions to demonstrate that Protearin is functionally equivalent to human plasma derived CLU and compare its efficacy to two reference compounds In addition planning activities for STTR Phase II will be performed including writing a protocol to transfer the process for Protearin production to a GMP lab and for adapting to GMP compliance identifying a qualified subcontractor for Good Laboratory GLP testing of GMP produced Protearin writing a protocol for a andquot first in humanandquot phase I clinical trial of Protearin the goal to assess product safty and provide proof of principal of efficacy in humans recruiting collaborators consultants and searching for new lab space for executing these next steps Most efforts for new drug development in the DE arena have been devoted to targeting of inflammation tear production tear film movement and tear chemistry i e factors located upstream in the cascade of events leading to DE and OCS disruption These factors differ and the various types of dry eye CLUandapos s action in sealing at the OCS has not been described for any other drug under development A therapeutic that can target upstream factors in dry eye as well as barrier disruption the final common endpoint represents an important innovation

PUBLIC HEALTH RELEVANCE Dry eye a group of disorders that affects million people over the age of in the USA today is characterized by inadequate hydration and lubrication of the ocular surface resulting in disruption of the ocular surface barrier In preliminary data usin a preclinical model it is shown that topical delivery of clusterin CLU a natural homeostatic tear protein prevents and ameliorates barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all or none threshold CLU binds selectively to the disrupted ocular surface barrier and positioned in this way it also protects barrier structure Te goal of Proteris Biotech Inc is to translate CLU to the clinic as an FDA approved biotherapeutic andquot Protearinandquot The innovation of Protearin is that it directly targets upstream effects of dry eye a well as barrier disruption the final common endpoint