Background

Microbial keratitis (infection of the cornea), which affects 840,000 people a year in India, is a common cause of corneal blindness. In low‑middle income countries, corneal ulceration, as a result of infection, results in 10,000 patients per year losing eyes which might otherwise be saved. Increasing use of contact lenses and corrective eye surgery is also leading to increases in keratitis.

Antimicrobial resistance in the causative organisms (e.g. P. aeruginosa) is rising and the use of broad-spectrum antibiotics as an empirical treatment is declining in effectiveness. Alternatives to traditional antibiotics are necessary to combat this problem.

The vital need for effective first line therapy for patients with early-stage eye infections has been identified by clinicians at LV Prasad Eye Institute (LVPEI) in Hyderabad, collaborators of The University of Sheffield.

Technology Overview

Researchers at The University of Sheffield have produced stapled peptides, derived from a human membrane protein, tetraspanin CD9, which have been shown to inhibit the adhesion of a range of pathogenic bacteria to epithelial cell lines in vitro. The peptides have shown anti-infective activities in vivo and can promote corneal wound healing.

Mechanism of Action: The peptides work by binding to host cell membranes disrupting a complex formed by host proteins that are involved in bacterial adherence. This disruption prevents the adhesion of bacteria to the host cell membrane and should not lead to antimicrobial resistance.

Efficacy: We have data demonstrating the anti-infective activity of the peptides at nanomolar concentrations in a mouse in vivo bacterial keratitis model, using an aggressive clinical isolate of P. aeruginosa. Here, treatment with a single dose of peptide reduced the load of bacteria in wounded and infected eyes by >99.9%, a 3-log reduction after 24 hours (considered a clinically relevant reduction). Peptide treatment also resulted in reduced corneal opacity, suggesting that the action of the peptides can reduce the onset of corneal blindness caused by bacterial infection. The anti-infective efficacy of the peptides has also been demonstrated in infection models using corneal cell lines and human corneal explants, as well as a 3D model of human skin and an in vivo mouse skin model.

The peptides showed beneficial effects on corneal wound healing, as assessed in the in vivo mouse model. Wounded eyes, treated with the peptide, showed healing in 80% of cases compared to very little healing in untreated eyes, suggesting that the peptides can promote re-epithelization of the cornea.

Benefits

Potent antimicrobial properties
Non-antibiotic approach to combat antimicrobial resistance: the host-directed mechanism means that the pathogen is unlikely to acquire resistance
Wound healing properties which are not exhibited by other antimicrobial approaches
Good stability of the peptide against proteolytic degradation due to the presence of stabilising staples
Good safety as demonstrated in the effect of the peptide on inflammation and cytokine profiles in in vivo models
Good storage stability as lyophilized peptides and in solution
Established relationship with institute in low‑middle income country

Applications

Treatment for traumatically wounded corneas
Post-surgical prophylactic treatment in LASIK and ophthalmic surgery (e.g. corneal transplantation)
Contact lens solution additive to heal microabrasions and prevent infection
Topical treatment for epithelial wounds and infections of the skin, e.g diabetic skin wounds
Prevention of biofilms
Surgical washes to reduce the risk of infection

Opportunity

The University is seeking an industrial partner to licence the technology or co-develop a new anti-infective therapy, based on this peptide technology, for the treatment of corneal or skin injuries.

The team’s academic expertise, intellectual property and access to clinically relevant models, as well as the clinical expertise of collaborators at LVPEI, would make the University a valuable development partner.

Peptide with Anti-infective and Wound Healing Properties for Corneal and Skin Applications

Patents

IP Status

Seeking