The University of Sheffield

Overview:
The University of Sheffield is a world top-100 university renowned for the excellence, impact and distinctiveness of its research-led learning and teaching. The University’s outstanding performance for excellent teaching and research, as part of a genuinely global community, is consistently confirmed by international independent assessments.
The university takes its public and social responsibility seriously. It is committed to making the world a better place. This approach is embedded in everything they do, from partnerships with local and global organisations to their research and teaching.
Research:
The University of Sheffield has a global reputation for world-leading research that makes a difference. It influences policy, changes lives and helps in understanding the world so that we can make it better. The university has over 180 research institutes, centres and groups. They address challenges from finding a cure for motor neurone disease to building a sustainable economic recovery. The research institutes and centres at the university have been created to address global challenges facing society, today and in the future. They are often interdisciplinary, with external collaboration and funding, and have earned international recognition.
The world-class research being undertaken at the University of Sheffield generates a wealth of new knowledge, much of which has the potential for licensing to innovative organisations seeking to augment their current activities or diversify their operations.
Industry Partnerships:
The University of Sheffield is collaborating with partners in the private, public and third sectors to find real-world solutions to real-world problems.
The university partners with organisations large and small, believing that by working together, we can find novel solutions to real-world problems. In their experience, it leads to world-class research and commercial success to businesses around the world. Together, The University of Sheffield shares knowledge, facilities and industry insight to help influence cultural, social, economic and political change.

<h1 id="background">Background</h1>
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.
<h1 id="technology-overview">Technology Overview</h1>
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 &gt;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.
<h1 id="benefits">Benefits</h1>
<ul>
<li>Potent antimicrobial properties</li>
<li>Non-antibiotic approach to combat antimicrobial resistance: the host-directed mechanism means that the pathogen is unlikely to acquire resistance</li>
<li>Wound healing properties which are not exhibited by other antimicrobial approaches</li>
<li>Good stability of the peptide against proteolytic degradation due to the presence of stabilising staples</li>
<li>Good safety as demonstrated in the effect of the peptide on inflammation and cytokine profiles in in vivo models</li>
<li>Good storage stability as lyophilized peptides and in solution</li>
<li>Established relationship with institute in low‑middle income country</li>
</ul>
<h1 id="applications">Applications</h1>
<ul>
<li>Treatment for traumatically wounded corneas</li>
<li>Post-surgical prophylactic treatment in LASIK and ophthalmic surgery (e.g. corneal transplantation)</li>
<li>Contact lens solution additive to heal microabrasions and prevent infection</li>
<li>Topical treatment for epithelial wounds and infections of the skin, e.g diabetic skin wounds</li>
<li>Prevention of biofilms</li>
<li>Surgical washes to reduce the risk of infection</li>
</ul>
<h1 id="opportunity">Opportunity</h1>
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.