A new trial receives significant funding to determine whether a drug, originally approved for use in the treatment of alcohol dependency, could have benefit for patients with eye scarring conditions.
Researchers from the University of Birmingham and Moorfields Eye Hospital have been awarded a £1.2million Medical Research Council (MRC) Experimental Medicine Grant to test whether oral disulfiram has an impact on conjunctival scarring in a rare blinding autoimmune disease, called ocular mucous membrane pemphigoid (OcMMP).
The initial discovery came from research led by a team at Moorfields Eye Hospital and the UCL Institute of Ophthalmology collaborating with UCL Royal Free and Duke University North Carolina, with the patient component (phenotyped tissue for in vitro studies from diseased subjects and healthy controls) supported by NIHR Moorfields Biomedical Research Centre (and funded by Fight for Sight UK). The University of Birmingham has subsequently led on this project, taking it to this next phase in humans and has been able to show the inflammation and scarring processes can be detected by analysing eye swabs and tears enabling these to become readouts of clinical trials.
This MRC funded trial will see oral disulfiram administered in tablet form, at the UK licensed dose, for a two-week interventional course in patients with OcMMP. Researchers will measure ALDH levels in tear samples to determine whether it is able to switch off ALDH in the conjunctiva. A swab and a sophisticated genetic test using a nanostring fibrosis panel will tell researchers whether the scarring process is affected by taking the tablet.
It is thought this study will be a first step towards developing a disulfiram anti-scarring eyedrop, because oral use of disulfiram is not recommended long term. A second grant from Sight Research UK, will allow researchers to understand the best disulfiram anti-scarring eye drop preparation to progress to a clinical trial of patients with OcMMP.
“Our goal is to reduce the burden of sight-loss from not only OcMMP, but also to explore the use of the anti-scarring eyedrop therapy in other disorders. These include chronic ocular Stevens-Johnson Syndrome, ocular Graft-versus-Host-Disease and glaucoma drug associated conjunctival scarring. There is also potential for major step-change transformation of patient care in lower and middle-income countries, where diseases such as trachoma (an infection that causes conjunctival scarring and the largest cause of preventable worldwide blindness) are prevalent.” explains Professor Saaeha Rauz, Institute of Inflammation and Ageing and Consultant Ophthalmologist at the Birmingham and Midland Eye Centre.
Professor Nicholas Barnes from the Institute of Clinical Sciences added ‘The research has already forwarded a specific isoform of ALDH as the molecular target for disulfiram. A longer-term goal of the research programme is to generate novel drugs to inhibit selectively this ALDH isoform, which we hope will deliver therapeutic benefit without some of the challenges that complicate the use of disulfiram’.
Dr Jose R Hombrebueno, from the Institute of inflammation and Ageing confirmed 'The team continues to explore the mechanisms underpinning OcMMP at the molecular level. In addition to ALDH, we hope to increase the number of therapeutic targets available to improve the standard of care in this and other related progressive conjunctival scarring conditions’.
The fact that there might be a solution to directly target the eye scarring progression is incredibly exciting. OcMMP takes peoples sight and does it with the maximum pain. A drop that could be used immediately to limit or even stop it? I can only imagine how radically different my own life would be if it had been around 20 years ago.Mark Noble, Patient of Bristol Eye Hospital and PEM Friends UK Member
The repurposing of licensed drugs in clinical trials is becoming more popular as it allows the trial to jump ahead past the most basic safety tests and could potentially see new treatments brought to market sooner.
The University of Birmingham researchers work in close partnership with the Birmingham and Midland Eye Hospital (Sandwell and West Birmingham NHS Trust), currently celebrating its bicentennial year. This work and other research projects from the University of Birmingham will be showcased at the Bicentennial BMEH Scientific Conference in December.