Impact of Oral Disulfiram on Aldehyde Dehydrogenase (ALDH) Mediated Ocular Fibrosis in Mucous Membrane Pemphigoid (OcMMP)
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Inflammation and Ageing
Abstract
Conjunctival scarring results from many diseases. These include trachoma, an infection that is known to be the largest cause of preventable blindness worldwide. It causes irreversible sight-loss in both eyes in 1.9 million worldwide. In the UK, the most common cause is a rare autoimmune driven disorder called Ocular Mucous Membrane Pemphigoid (OcMMP) that occurs in 0.8 people in a million population each year. OcMMP creates chronic inflammation and scarring of the conjunctiva which lines the inside of the eyelids and covers the white of the eye. Scarring of the inside lining of the eyelid can cause the lashes to turn inwards and scratch the cornea (trichiasis). This and inflammation, lead to debilitating symptoms of constant irritation, pain, and dryness. Treatments involve immunosuppression but this has little effect on scarring. For half of patients, scar formation continues; 20% become irreversibly blind.
Our research on conjunctival tissue taken from patients with OcMMP whilst undergoing diagnostic conjunctival biopsies as part of their routine clinical care, and in our ocular pemphigoid-like mouse model, has shown that the enzyme, aldehyde dehydrogenase (ALDH), controls conjunctival scarring both in OcMMP human tissue and in the pemphigoid mouse. Disulfiram (DSF; a drug used as a tablet given by mouth for alcohol-abuse treatment) permanently blocks ALDH action. We have found that DSF has anti-inflammatory and anti-scarring properties and when given to the pemphigoid-like mouse in an eyedrop form (once daily for one week), DSF reverses inflammation and scarring.
We would like to understand whether disulfiram has the same mechanism of action if given to patients with OcMMP. As there is no licensed disulfiram eyedrop formulation, we would like to give tablets by mouth at the UK licensed safe dose, to patients with OcMMP for two weeks and examine how it effects the scarring signals in the conjunctiva. We will do this by taking swabs, tear and blood samples from patients before starting treatment, one week into treatment, at the end of treatment and two weeks after coming off treatment.
Previously, we have taken conjunctival swabs from patients with and without OcMMP and have shown that we can detect key players in the mechanisms of conjunctival scarring at a genetic level using a technique called nanostring. Nanostring allows us to detect a large number of genes from one swab. We have identified a cluster of genes known to be part of the scarring pathway that are abnormal in OcMMP patient conjunctiva.
Importantly, using a sensitive assay optimised by us, we have been able to quantify ALDH levels in tears and have shown ALDH activity to be around 10 times higher in patients with OcMMP compared to those who do not have the disease.
What this means is that we can test whether giving disulfiram tablets to patients with OcMMP switches off ALDH action in the conjunctiva (determined using tear samples) and whether this modifies the scarring process (assessed using conjunctival swabs). As inflammation drives scarring, and we know that the disulfiram eyedrop in the pemphigoid-like mouse reduced conjunctival inflammation, we will analyse the presence of inflammatory biomarkers both on the surface of the eye (using tears) and the bloodstream (using a blood sample) to see if taking disulfiram tablets can also reduce the associated inflammatory signals.
In this way, we anticipate we will generate sufficient information to support our hypothesis that ALDH is pivotal to the human conjunctival scarring pathway. As indefinite use of oral disulfiram should be avoided, this finding will encourage development of a novel disulfiram anti-scarring eyedrop to test as a treatment in clinical trials. Our goal is to improve the patient experience of living with OcMMP, and to transform patient care on a global scale by reducing the burden of sight-loss for this and other conjunctival scarring disorders.
Our research on conjunctival tissue taken from patients with OcMMP whilst undergoing diagnostic conjunctival biopsies as part of their routine clinical care, and in our ocular pemphigoid-like mouse model, has shown that the enzyme, aldehyde dehydrogenase (ALDH), controls conjunctival scarring both in OcMMP human tissue and in the pemphigoid mouse. Disulfiram (DSF; a drug used as a tablet given by mouth for alcohol-abuse treatment) permanently blocks ALDH action. We have found that DSF has anti-inflammatory and anti-scarring properties and when given to the pemphigoid-like mouse in an eyedrop form (once daily for one week), DSF reverses inflammation and scarring.
We would like to understand whether disulfiram has the same mechanism of action if given to patients with OcMMP. As there is no licensed disulfiram eyedrop formulation, we would like to give tablets by mouth at the UK licensed safe dose, to patients with OcMMP for two weeks and examine how it effects the scarring signals in the conjunctiva. We will do this by taking swabs, tear and blood samples from patients before starting treatment, one week into treatment, at the end of treatment and two weeks after coming off treatment.
Previously, we have taken conjunctival swabs from patients with and without OcMMP and have shown that we can detect key players in the mechanisms of conjunctival scarring at a genetic level using a technique called nanostring. Nanostring allows us to detect a large number of genes from one swab. We have identified a cluster of genes known to be part of the scarring pathway that are abnormal in OcMMP patient conjunctiva.
Importantly, using a sensitive assay optimised by us, we have been able to quantify ALDH levels in tears and have shown ALDH activity to be around 10 times higher in patients with OcMMP compared to those who do not have the disease.
What this means is that we can test whether giving disulfiram tablets to patients with OcMMP switches off ALDH action in the conjunctiva (determined using tear samples) and whether this modifies the scarring process (assessed using conjunctival swabs). As inflammation drives scarring, and we know that the disulfiram eyedrop in the pemphigoid-like mouse reduced conjunctival inflammation, we will analyse the presence of inflammatory biomarkers both on the surface of the eye (using tears) and the bloodstream (using a blood sample) to see if taking disulfiram tablets can also reduce the associated inflammatory signals.
In this way, we anticipate we will generate sufficient information to support our hypothesis that ALDH is pivotal to the human conjunctival scarring pathway. As indefinite use of oral disulfiram should be avoided, this finding will encourage development of a novel disulfiram anti-scarring eyedrop to test as a treatment in clinical trials. Our goal is to improve the patient experience of living with OcMMP, and to transform patient care on a global scale by reducing the burden of sight-loss for this and other conjunctival scarring disorders.
Technical Summary
OcMMP is an orphan disease characterised by chronic autoimmune-driven conjunctival inflammation leading to progressive scarring, debilitating symptoms and blinding sequelae. Systemic immunotherapy modifies inflammation but does not limit progression of fibrosis either in inflamed eyes, or in 50% of clinically quiescent eyes, leading to blindness in 20%. Understanding the pathogenic mechanism underpinning progressive conjunctival fibrosis will facilitate development of therapies for which there is a clear unmet clinical need.
Using gene expression in human OcMMP conjunctival tissue, we have shown that inhibition of the ALDH1A3 isoform is a candidate anti-fibrotic mechanism. This is supported by (i) structural and functional abnormalities of human OcMMP conjunctival fibroblasts that were normalised by ALDH inhibition in vitro, and (ii) prevention of conjunctival scarring and inflammation in a surrogate OcMMP mouse model.
Building on this, we aim to repurpose oral disulfiram (DSF) as a tool drug to interrogate the ALDH-mediated conjunctival fibrosis signalling pathway in patients with OcMMP. DSF is a non-sleective aldehyde dehydrogenase (ALDH) inhibitor with an established safety profile licensed for treatment of alcohol-abuse, yet would present clinical issues if used as a chronic oral therapy. Patients will receive DSF for just 2 weeks and ocular samples (tears, swabs) and peripheral blood analysed pre-, during and post-DSF with mechanistic outcomes assessed (including (i) ALDH inhibition in the tears as a readout of pharmacological engagement and, (ii) normalisation of pivotal profibrotic factors such as Collagen Type 1 as a biomarker predictive of efficacy).
Arising supporting data will provide confidence in our hypothesis that ocular ALDH inhibition can deliver local anti-fibrotic efficacy and hence encourage our development of a topical DSF formulation predicted to deliver clinical efficacy without systemic issues arising from chronic oral DSF.
Using gene expression in human OcMMP conjunctival tissue, we have shown that inhibition of the ALDH1A3 isoform is a candidate anti-fibrotic mechanism. This is supported by (i) structural and functional abnormalities of human OcMMP conjunctival fibroblasts that were normalised by ALDH inhibition in vitro, and (ii) prevention of conjunctival scarring and inflammation in a surrogate OcMMP mouse model.
Building on this, we aim to repurpose oral disulfiram (DSF) as a tool drug to interrogate the ALDH-mediated conjunctival fibrosis signalling pathway in patients with OcMMP. DSF is a non-sleective aldehyde dehydrogenase (ALDH) inhibitor with an established safety profile licensed for treatment of alcohol-abuse, yet would present clinical issues if used as a chronic oral therapy. Patients will receive DSF for just 2 weeks and ocular samples (tears, swabs) and peripheral blood analysed pre-, during and post-DSF with mechanistic outcomes assessed (including (i) ALDH inhibition in the tears as a readout of pharmacological engagement and, (ii) normalisation of pivotal profibrotic factors such as Collagen Type 1 as a biomarker predictive of efficacy).
Arising supporting data will provide confidence in our hypothesis that ocular ALDH inhibition can deliver local anti-fibrotic efficacy and hence encourage our development of a topical DSF formulation predicted to deliver clinical efficacy without systemic issues arising from chronic oral DSF.
Organisations
Publications

Harman K
(2023)
The top 10 research priorities for the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris in the UK: results of a James Lind Alliance Priority Setting Partnership
in British Journal of Dermatology

Panthagani J
(2023)
Conjunctival transcriptomics in ocular mucous membrane pemphigoid.
in The ocular surface


Title | Ocular Mucous Membrane Pemphigoid (OcMMP) Patient Recruitment | University of Birmingham |
Description | University of Birmignham YouTube Video Channel. |
Type Of Art | Film/Video/Animation |
Year Produced | 2024 |
Impact | The Ocular Mucous Membrane Pemphigoid (OcMMP) Patient Recruitment video, produced by the University of Birmingham, has played a crucial role in raising awareness about the MMP Oral-DSF Clinical Trial among patients, healthcare professionals, and the wider public. The video provides clear and accessible information about the trial's aims, eligibility criteria, and potential impact, helping to enhance patient engagement and recruitment efforts. By featuring expert insights and patient-centred messaging, it has contributed to improved understanding of ocular Mucous Membrane Pemphigoid (OcMMP) and the importance of clinical research in developing new treatment options. Additionally, the video has been shared across academic and clinical networks, increasing visibility and fostering interest in the trial among both national and international audiences. It has also supported ongoing patient and public involvement (PPIE) efforts, ensuring that those affected by OcMMP feel informed and empowered to participate in research. |
URL | https://www.youtube.com/watch?v=blQdzDJJkC0&ab_channel=UniversityofBirmingham |
Guideline Title | European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid Part II |
Description | European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical guidelines |
Impact | This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials. |
URL | https://onlinelibrary.wiley.com/doi/10.1111/jdv.17395 |
Guideline Title | European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid Part I |
Description | European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical guidelines |
Impact | This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course. |
URL | https://onlinelibrary.wiley.com/doi/10.1111/jdv.17397 |
Description | International Corneal and Ocular Surface Disease Dataset for Electronic Health Records |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | Changes Arising from this Influence on Policy, Practice, Patients, or the Public: The development of a **comprehensive and internationally standardised Cornea and Ocular Surface Disease (C&OSD) dataset** has led to several key changes in **policy, clinical practice, and research**: ### **1. Improved Clinical Documentation and Patient Care** - The **structured dataset** enables **consistent and efficient data entry** in **electronic health records (EHRs)**, improving **diagnosis, treatment planning, and monitoring** of C&OSD patients. - The inclusion of **gateway disease categories** (e.g., dry eye, keratoconus, cicatrising conjunctivitis) ensures a **streamlined approach to patient assessment**. ### **2. Enhanced Research and International Collaboration** - The dataset supports **standardised data collection** across institutions and countries, enabling **large-scale clinical audits and research studies**. - Researchers can now **compare outcomes internationally**, leading to **evidence-based advancements** in ophthalmology. ### **3. Policy and EHR System Integration** - The dataset aligns with **Royal College of Ophthalmologists guidelines**, ensuring **compliance with best practices**. - Adoption by **EHR providers** enhances **data interoperability** across healthcare systems, improving **cross-institutional patient care**. ### **4. Public and Patient Benefits** - More **accurate and complete patient records** lead to **personalised treatment approaches** and **better long-term eye health outcomes**. - Standardised data collection supports **patient-reported outcome measures**, giving **patients a voice in their care**. ### **Evidence of Reach and Benefit:** - **35 international experts** contributed to the dataset, ensuring **global applicability**. - Integration with **existing clinical registries** (e.g., Dry Eye Workshop II, UK Transplant Registry) demonstrates **broad adoption potential**. - Improved **EHR standardisation** supports **multi-center clinical trials** and **real-world evidence generation** for C&OSD treatments. This initiative **sets a new benchmark for ophthalmic data collection**, leading to **better patient outcomes, enhanced research opportunities, and stronger global collaboration** in cornea and ocular surface disease management. |
URL | https://pubmed.ncbi.nlm.nih.gov/39974104/ |
Description | The Royal College of Ophthalmologists: Corneal and Ocular Surface Disease Dataset |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in other policy documents |
Impact | The Royal College of Ophthalmologists (RCOphth) has developed standardized clinical datasets to enhance data collection and analysis in ophthalmic care. These datasets have significantly improved policy, clinical practice, and patient outcomes. Standardized data recording across ophthalmic practices ensures consistent clinical documentation, leading to better patient assessments, treatment planning, and continuity of care. The National Ophthalmology Database (NOD) audit, for example, collects data on cataract surgeries, enabling benchmarking and the identification of best practices. Comprehensive data collection allows for detailed analysis of eye health trends, aiding policymakers in making informed decisions. The Office for Health Improvement and Disparities has published a refreshed Vision profile, detailing eye health data up to 2021/22, which provides clinicians with tools to compare patient profiles and unit performance across various metrics. This information supports the case for appropriate resourcing of ophthalmology services and ensures that healthcare provision aligns with patient needs. The NOD also serves as a valuable resource for audit and research, contributing to the development of quality standards and the revalidation of ophthalmologists. Research using NOD data has provided insights into outcomes of vitrectomy procedures for proliferative diabetic retinopathy, leading to evidence-based improvements in surgical practices. Standardized data collection enhances patient safety by identifying risks and enabling the implementation of preventive measures. The RCOphth has provided guidance to improve ophthalmic patient safety, detailing which incidents should be reported and analyzed in practice. This has led to increased awareness and proactive safety measures in ophthalmic care. The reach and impact of these datasets are evident through extensive engagement in the NOD audit, which has collected data from over one million cataract operations, involving more than 350 surgeons across the UK. By ensuring consistency in clinical documentation, informing policy decisions, advancing research, and improving patient safety, these standardized datasets have set a new benchmark for ophthalmic care, ultimately leading to better patient outcomes and more efficient healthcare services. |
URL | https://www.rcophth.ac.uk/resources-listing/clinical-datasets/ |
Guideline Title | Treatment of Pemphigus and Pemphigoid PSP protocol |
Description | The top 10 research priorities for the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris in the UK: results of a James Lind Alliance Priority Setting Partnership |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical guidelines |
Impact | The Priority Setting Partnership (PSP) for Bullous Pemphigoid (BP), Mucous Membrane Pemphigoid (MMP), and Pemphigus Vulgaris (PV) has influenced policy, practice, and research by identifying the top 10 research priorities in the treatment of these autoimmune blistering diseases. Changes Arising from this Influence: 1. **Research Funding & Direction:** - The identified priorities guide researchers and funders to focus on patient- and clinician-relevant questions, ensuring that future studies address the most pressing treatment uncertainties. - The **Medical Research Council (MRC) grant** for investigating disulfiram in MMP is an example of research influenced by patient and clinician priorities. 2. **Clinical Practice Improvements:** - Increased awareness among dermatologists, ophthalmologists, and oral medicine specialists about shared treatment challenges across BP, MMP, and PV. - Potential future improvements in treatment guidelines based on research addressing these priorities. 3. **Patient & Public Involvement (PPI):** - The engagement of **patients, carers, and healthcare professionals** in the PSP has led to a **more patient-centered research agenda**, improving trust and collaboration between researchers and the public. ### **Evidence of Reach and Benefit:** - **258 initial respondents** (166 patients/carers, 92 healthcare professionals) helped generate **974 research questions**, later refined into **46 indicative questions** and finally the **top 10 priorities** through surveys and a consensus workshop. - **PEM Friends UK, professional organizations, and social media** played a key role in raising awareness and ensuring widespread participation. - The **University of Birmingham-led research on disulfiram** aligns with the PSP's goal of improving treatments and could lead to **new therapies for conjunctival scarring diseases.** This initiative has set a foundation for future clinical trials, policy changes, and treatment advancements that will **benefit patients, influence clinical guidelines, and improve care quality** for those with BP, MMP, and PV. |
Description | Impact of Oral Disulfiram on Aldehyde Dehydrogenase (ALDH) Mediated Ocular Fibrosis in Mucous Membrane Pemphigoid (OcMMP) |
Amount | £1,247,762 (GBP) |
Funding ID | MR/X0191951 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2023 |
End | 09/2025 |
Description | Sustained Delivery of Anti-fibrotic Agents for Ocular Mucous Membrane Pemphigoid |
Amount | £150,000 (GBP) |
Funding ID | TRN 001 |
Organisation | Sight Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2023 |
End | 10/2025 |
Title | TREATMENT OF FIBROSIS |
Description | The present invention relates an aldehyde dehydrogenase inhibitor for use in the treatment or prevention of fibrosis. |
IP Reference | WO2015166277 |
Protection | Patent / Patent application |
Year Protection Granted | 2015 |
Licensed | No |
Title | An experimental medicine trial evaluating oral disulfiram repurposed to probe the ALDH mediated profibrotic mechanism in ocular disease (MMP-Oral-DSF) |
Description | The study targets 30 adults (aged 16+) with OcMMP, a condition where scarring progresses in 50% of uninflamed eyes, potentially leading to blindness in 20% of cases. Patients will have moderate/mild inflammation (grade =2) without changes in systemic/ocular therapy for over 3 months to avoid confounding results. The goal is to achieve 50% downregulation of ALDH activity in at least 60% of treated eyes. The study is divided into two stages. In Stage 1, 10 participants undergo a 42-day study consisting of a 14-day pre-treatment phase, a 14-day treatment phase with oral disulfiram, and a 14-day post-treatment phase. In Stage 2, if Stage 1 is tolerable and ALDH activity is reduced in at least one eye, 20 more participants are recruited. The disulfiram dosage includes a loading dose of 600 mg on Day 1, followed by a maintenance dose of 200 mg daily from Days 2 to 14. If intolerable (=4 dose-limiting events), the dose is reduced to 100 mg daily. If still intolerable, the study is discontinued. Participants have 6 weekly in-person visits and 12 daily virtual reviews during the treatment phase. Safety is monitored throughout, with unscheduled DMC meetings for any unexpected serious adverse reactions. The primary outcome is ALDH inhibition in tears, indicating fibrosis prevention. Secondary outcomes include reduced conjunctival profibrotic gene expression, reduced pro-inflammatory/profibrotic cytokines, and systemic ALDH inhibition to ensure compliance. Exploratory outcomes involve ocular microbiome analysis, bacterial diversity changes, and neutrophil phagocytosis activity. Disulfiram is chosen for its established safety profile and efficacy in inhibiting ALDH, with potential to reduce fibrotic activity. Its use in this study could provide proof-of-concept for developing a targeted topical therapy. The study uses the clinically licensed oral form of Disulfiram (Antabuse), approved in the UK since 1994, following a regimen similar to its use in treating chronic alcoholism. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2024 |
Development Status | Actively seeking support |
Impact | This project aims to repurpose oral disulfiram, a well-established and utilised medication in clinical medicine, to interrogate ocular scarring pathways and assess whether ALDH inhibition can abrogate an ALDH-mediated (via retinoic-acid - an ALDH metabolite) enhanced mucosal scarring process. Establishing this information via an oral-based experimental intervention would be encouraging to create novel topical therapeutics containing disulfiram (for which there are currently none) to be assessed in future trials for patients with OcMMP. |
Description | PEMFriends PPIE Event: "Insights into the pemphigoid oral disulfiram study" |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | The PPIE event for the **MMP Oral-DSF Clinical Trial** engaged individuals affected by **Mucous Membrane Pemphigoid (MMP)**, patient advocacy groups, and clinical researchers to discuss the impact of **oral disulfiram on aldehyde dehydrogenase-mediated ocular fibrosis**. The session aimed to provide insight into the trial's objectives, methodology, and potential benefits while ensuring that patient perspectives were incorporated into the research process. The event facilitated an open discussion on the treatment challenges faced by MMP patients, allowing researchers to refine aspects of the trial based on real-world concerns. Participants gained a clearer understanding of the ongoing research, fostering engagement and trust in clinical research. Feedback gathered helped shape the trial's patient information materials, ensuring accessibility and relevance. Increased awareness among attendees contributed to broader discussions on the need for innovative treatments for ocular fibrosis in MMP. |
Year(s) Of Engagement Activity | 2025 |
Description | PEMFriends: "In Search of Scar Prevention for Patients with Ocular Pemphigoid: The MMP Oral Disulfiram Study" |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | On January 23, 2025, Professor Saaeha Rauz and her team from the Academic Unit of Ophthalmology, Birmingham and Midland Eye Centre, University of Birmingham, presented their research on ocular pemphigoid in a Zoom talk hosted by PEM Friends. The talk highlighted decades of work aimed at understanding conjunctival scarring and developing potential treatments. The discussion covered key aspects of the Medical Research Council Experimental Medicine Grant-funded study, including clinical background, laboratory findings, and the rationale behind using disulfiram-a drug typically used to treat alcohol dependency-to inhibit aldehyde dehydrogenase (ALDH), an enzyme implicated in the scarring process. The event provided PEM Friends members with a unique opportunity to engage with researchers and learn about the ongoing clinical trial investigating oral disulfiram. The study aims to understand the molecular effects of disulfiram and will pave the way for the development of disulfiram eye drops, potentially reducing side effects while offering a new treatment option for conjunctival scarring. |
Year(s) Of Engagement Activity | 2025 |
URL | https://www.pemfriends.org.uk/talks-from-experts/rauz |
Description | PEMFriends: "PEM Lives Issue No:10 - December 2024" |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Researchers at the University of Birmingham have received a £1.2 million Medical Research Council (MRC) Experimental Medicine Grant to investigate the effects of oral disulfiram on ocular mucous membrane pemphigoid. The study aims to assess whether disulfiram, originally used to treat alcohol dependency, can reduce progressive conjunctival scarring by inhibiting the enzyme aldehyde dehydrogenase (ALDH). Participants with ocular pemphigoid will take disulfiram for two weeks and undergo eye and immune system assessments over a 42-day period. The Birmingham and Midland Eye Centre, the lead NHS site, plans to begin recruiting UK-based patients in November 2024, alongside a Launch Webinar with PEM Friends. The research builds on previous findings funded by Fight for Sight, involving collaborations between UK and US institutions. It has the potential to improve treatments for other scarring-related eye diseases, such as Stevens-Johnson Syndrome, ocular Graft-versus-Host Disease, and trachoma, a leading cause of preventable blindness worldwide. Expected impacts include improved treatment options for patients, reduced sight loss, and the development of new drugs targeting specific ALDH isoforms. The study offers hope for better patient outcomes and could significantly advance ophthalmic care, particularly in lower- and middle-income countries. |
Year(s) Of Engagement Activity | 2024 |
URL | https://www.pemfriends.org.uk/_files/ugd/ab0c71_300105330109455f8136fc48946dd923.pdf |
Description | University of Birmingham: News |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | A press release was published by the University of Birmingham to raise awareness of the MMP Oral-DSF Clinical Trial, which is investigating the potential of an existing drug, disulfiram, as a treatment for ocular fibrosis in Mucous Membrane Pemphigoid (MMP). The article provided an overview of the trial, highlighting its aims, scientific rationale, and potential impact on patients with this rare blinding autoimmune disease. The publication helped to increase public and professional awareness of the trial, supporting patient recruitment and engagement. It also contributed to knowledge exchange within the research and clinical community, potentially fostering further collaborations and discussions around repurposing existing drugs for rare diseases. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.birmingham.ac.uk/news/2023/existing-drug-being-tested-for-new-use-in-patients-with-a-rar... |