A transformative treatment for Ocular Mucous Membrane Pemphigoid (OcMMP)
- Grant holder: Saaeha Rauz, Professor in Translational Ophthalmology
- Institution: University of Birmingham
- Grant award: £150,000
- Start: November 2022
- End: October 2024
What is OcMMP?
Ocular Mucous Membrane Pemphigoid (OcMMP) is an autoimmune disease that causes chronic inflammation and progressive scarring of the conjunctiva - the clear membrane that covers the white of the eye and the inside of the eyelids.
Most people will experience conjunctivitis at some point in their lives, and will be familiar with its symptoms: a red and sticky eye that feels sore and irritated. Conjunctivitis usually resolves on its own or can be treated easily, but for people with OcMMP, the condition is persistent and recurrent. It does not respond to antibiotics or eye drops and can cause debilitating pain and irritation.
As the inflammation and scarring progress, they can cause the eyelids to turn inwards so that the eyelashes scratch the surface of the eyes. This in turn can damage the cornea – the transparent outer layer of the front of eye, which protects the eye from damage and infection and helps to focus light. The scarring and inflammation can also affect the tear ducts, causing severe dry eyes, which compound the discomfort.
Why is this research needed?
As currently available topical treatments – those put directly into the eye – are ineffective in 80% of patients, most people with OcMMP are treated with immunosuppressive drugs. These are designed to reduce the overactivity of the body’s immune system, which drives the inflammation and scarring, but their effectiveness is limited. This means that for half of all people with OcMMP, scar formation continues – and one in five people will become irreversibly blind.
Saaeha Rauz, Professor in Translational Ophthalmology at the University of Birmingham, is leading a well-established research team that has been studying the mechanisms of scarring in OcMMP since 2003, in collaboration with Professor John Dart (Moorfields Eye Hospital). They were the first in the world to discover that an enzyme, aldehyde dehydrogenase (ALDH), plays a key role in the scarring process. This was a major breakthrough because it pointed the way to suggesting how the disease might be better treated.
The team subsequently discovered that a drug, disulfiram, which is currently used to treat alcohol dependency, is successful at blocking ALDH. However, disulfiram has very unpleasant side effects when taken orally, and also has low solubility. This means that in a conventional eye drop, only about 1/100thof the drug can be absorbed into the eye before being lost by tear washout.
What is the aim of the project?
In order to combat these problems, Professor Rauz is developing a revolutionary gel-based eye drop in which to package the disulfiram. The gel-system thins on blinking, releasing the drug, then forms a soft protective coating when the eyes are open. It is hoped that this will enable the drug to stay in contact with the surface of the eye longer than is the case with conventional drops, allowing better penetration into the conjunctiva, and greatly improving its ability to supress inflammation and scarring.
The aim of this project is to manufacture and test a series of anti-scarring eye drop formulations to determine the optimal dose. The formulations will be tested for their effectiveness in treating scarring, their safety, and to ensure that they do not cause harmful side effects.
How will this research help people with OcMMP faster?
The data gathered from this project will be key to enabling the research to progress to the next stage - clinical trials in small groups of patients.
While Professor Rauz’s ultimate goal is to improve the quality of life for people with OcMMP, she is very hopeful that the anti-scarring eyedrop therapy could be expanded to treat related conditions that cause similar symptoms, such as Stevens-Johnson Syndrome, a disorder of the skin and mucous membranes, and Graft-versus-Host Disease, a complication of transplant surgery.
Importantly, the proposed new treatment offers great potential to help people who suffer conjunctival scarring as a side-effect of treatment for glaucoma, a leading cause of blindness globally that affects some 500,000 people in the UK alone.
Ocular Mucous Membrane Pemphigoid (OcMMP) is one of a group of autoimmune diseases - Pemphigoid, Pemphigus and some related conditions - that affect the skin and other mucous membranes of the body. If you are looking for further information about living with these conditions, PEM Friends can help. Founded in 1999, they are a group of patients and their carers who provide support and advice to people diagnoses with Pemphigus or Pemphigoid and those who care for them.
A heartfelt thank you to everyone who gave through the BigGive Christmas Challenge 2021, and especially to The Hospital Saturday Fund. Your donations are helping to make this research possible and we could not be more grateful for your support.
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