University of Pittsburgh researchers have developed a novel slow release approach to deliver therapeutic peptides to the eye. Using coacervate derived from PEAD (poly(ethylene argininylaspartate diglyceride)) and heparin with a key peptide – CXCL10p, known to activate the CXCR3 receptor and which may preserve and possibly regenerate goblet cells – the therapy can be released at a tunable rate into the eye. This approach could allow for the daily, weekly, or monthly application of a gel, topical drop, cream, or subconjunctival injection, to deliver therapy for dry eye disease (DED) improving treatment compliance and comfort in patients.
Following three weeks of treatment with a coacervate-based gel containing peptides known to activate the CXCR3 receptor, signs of DED in animals were reduced. Tear break up time (TBUT) was restored to levels before induction of DED. The gel allows for controlled release of treatment for DED, requiring less applications, and has the potential to improve regimen compliance, allowing for direct treatment of the underlying cause of DED.
Description
DED, where the eyes no longer retain the tears on the eye surface to protect the eye from the elements, affects 16 million Americans and as many as 1 in 4 people in some countries. Left untreated, DED can result in infections to the sclera and damage to the cornea and blindness in severe cases. Goblet cells secrete the mucins that keep the ocular surface wet and maintain tear films. The loss of goblet cells is currently an irreversible step in the progression of DED. There is an urgent clinical need to develop treatments to prevent loss of goblet cells and the associated development of DED. The peptide CXCL10p can activate the CXCR3 receptor which plays a crucial role in preventing goblet cell loss. Integrating these peptides into a coacervate gel leads to controlled, sustained release of medication into the eye and could provide a novel treatment approach for DED and other eye diseases.
Applications
• Dry eye disease
Advantages
Current treatments for DED involve treating only the symptoms and do not deal with the cause of the disease. Treatment involves the application of artificial tears to the eye multiple times per day and can be uncomfortable and time-consuming for patients. This novel approach uses a CXCL10p-coacervate conjugated peptide to promote the health of goblet cells, targeting the underlying cause of DED. The peptides can be formulated to make drops or creams that patients can self-administer. This treatment provides prolonged delivery of medication to the eye and removes the need for frequent application while providing immediate symptomatic relief. Additionally, this formulation can also be used as an injectable, allowing clinicians to deliver targeted in-clinic treatment.
Invention Readiness
Three studies in animals with DED haves been performed. These involved both chemically- and surgically-induced DED (about 10% of all DED) and environmentally-triggered DED (>70% of DED). In all three studies the eye surface was improved back to baseline, whereas the control groups demonstrated continued damage to the eye surface. In one environment study, rabbit eyes were treated topically with sterile PBS (control), drops or a coacervate gel containing CXCR3 activating peptides in both eyes, twice a day, for three weeks. A fourth group had subconjunctival injections containing key peptides on days 1, 7, and 14. All treatments alleviated the corneal haze and punctuate corneal haze in addition to other anomalies that characterize DED. Compared with the control arms, treatment with the gel and subconjunctival injection significantly improved TBUT levels and even resulted in TBUT levels above those observed prior to DED induction in the animals.
IP Status
https://patents.google.com/patent/WO2024118744A2
