MDI Research
MDI has a history of funding and supporting neuromuscular research. We believe that research is the most beneficial way to improve understanding of the conditions and we support research and researchers in a variety of ways. This includes support with recruitment to studies, disseminating research findings, collaborating with academic institutions and pharmaceutical industries, and using research to advocate for improved services and supports for people living with neuromuscular conditions in Ireland.
A member survey in 2014 and again in 2023 highlighted research as an important area of interest for the community. To meet this need, in recent years MDI employed a full-time research officer to grow the research arm of the organisation. The strength of the research committee has also grown to include expert members as well as lay members who abide under an agreed Terms of Reference.
In recent years MDI has prioritised activities that are essential to manage MDI’s research department effectively. These include:
To identify and oversee the strategic direction of MDI’s research resources in consultation with the Board of Directors, the Research Committee, and the Members of MDI.
Broaden the scope of topics covered by MDI research to include both social, and medical research.
Development of policies surrounding MDI research.
Manage and develop relationships with researchers, and monitor the progress of collaborative projects, to ensure they meet their agreed endpoints.
Develop relationships with pharmaceutical companies.
Embed Patient and Public Involvement (PPI) into research activities and support members of the community to be involved in PPI opportunities.
Complete a scoping review for the development of a neuromuscular disease registry in Ireland.
Research Strategy
In 2023 MDI released its first robust Research Strategy for 2023 – 2025. This ambitious plan will guide and direct activities for the duration of the strategy. It will ensure MDI has strong research processes and procedures for ongoing future activities.
Research Priorities:
MDI’s Research Strategy for 2023 - 2025 focuses on three priority areas;
Support the development of essential research infrastructure for neuromuscular research in Ireland;
Encourage and support solution focused research which will lead to improvements in quality of life, including use of aids and smart technology and development of therapies for people living with neuromuscular conditions;
Translate and disseminate advances in research to promote awareness, encourage research activity and exchange of knowledge.
To fulfil these priorities, several objectives and outputs have been identified. These are underpinned by four principles (Plan, Partner, Participate, Promote,) which are embedded and interconnected throughout the strategic plan.
View MDI’s Research Strategy in full
Research Committee
The Research Committee advises MDI’s Board of directors on all matters relating to research. On behalf of people living with neuromuscular conditions, the committee supports the organisation in areas relating to neuromuscular research.
The committee is composed of individuals with lived experience of a neuromuscular condition, clinicians, researchers, and others with a specialist interest in neuromuscular conditions in addition to representatives from MDI (MDI CEO and MDI Research Officer).
Members of the Research Committee
Dr Ashling Holland – Research Committee Chairperson
Dr Stela Lefter
Dr Imran Sulaiman
Dr John Porter
Jaap De Boer
Dr Eoghan Clifford
Michael Maher
Marie Loughlin
Aoife Mc Nicholl
Dympna Mulroy – MDI Research Officer
Alan Breathnach – MDI CEO
Past Projects
Since 2002, MDI has contributed over €400,000 towards innovative projects including biomedical, preclinical, clinical, and quality-of-life focused research.
MDI has collaborated on co-funding opportunities to include the Health Research Board and the Irish research Council. The further investment from external funders can only be made possible by the continued identification of funding sources and application for these opportunities in a competitive environment.
MDI know the importance of using research findings to lobby for better services and conditions for its members. We ensure the research we support aligns with our organisational strategy and is impactful towards the lives of those living with a neuromuscular condition.
Research Collaborations
The above graph illustrates the range of projects MDI has supported. This collaboration may have been financial, co-designing, assisting with recruitment, sharing resources, supporting patient and public involvement and dissemination of findings.
A summary of these studies are outlined below.
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Dr Julie Broderick (supervisor), final year project Discipline of Physiotherapy, Trinity College Dublin
Perceptions of people with Muscular Dystrophy towards physiotherapy services.
Click here for a summary of Dr. Broderick’s study.
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Siobhan O Shea and Dr Michelle Spirtos; Discipline of Occupational Therapy, Trinity College Dublin
Supporting Transitions to Adulthood Resources (STAR) Project.
Recruitment closed. Results will be published early 2025.
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Brona Mulligan, Dr Oonagh Meade, and Márcia Filipa; School of Psychology, University of Galway
The lived Experience of Health-Related quality of Life for Adults with Muscular Dystrophy.
A summary of the results is viewable here.
For a more detailed report, Click here.
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Dr Finiki Nearchou, University College Dublin, School of Psychology
The psychosocial needs of adults living with muscular dystrophy and similar genetic neuromuscular disorders.
Read Dr. Nearchou’s full report and findings of the study here.
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Prof. Eileen Gibney (Supervisor), Ciaran Kelly (student); Institute of Food and Health, University College Dublin
Assessment of the Knowledge of the Nutritional Management of Muscular Dystrophy among Dietitians, Nutritionists, and other Health Care Professionals.
This study, aimed to examine the knowledge of the nutritional management of muscular dystrophy among health care professionals, specifically dietitians and nutritionists, to determine knowledge gaps and areas required for training. A survey was designed to determine healthcare professional knowledge of a variety of different areas including energy provision, macro and micronutrients of concern and morbidities associated with muscular dystrophy. Results from the survey determined a low level of knowledge across all aspects of nutrition management of muscular dystrophy. Further exploration into these knowledge gaps with the aim of producing fact sheets and webinar topics to increase the confidence and knowledge among health care professionals, was recommended.
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PTC Therapeutics
‘Transition in DMD; Teenager, Young Adult and Caregiver Experience’ European survey.
Click here for a summary of the results of the PTC Therapeutics study
View poster image of results
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Dr Julie Broderick (supervisor), final year project Discipline of Physiotherapy, Trinity College Dublin
The role of physiotherapy in the management of Muscular Dystrophies: an online survey among physiotherapists working in Irish healthcare settings.
This study indicates physiotherapists generally treat people with muscular dystrophy as part of a mixed caseload in a variety of settings. A clear training need was identified, which may also be applicable to other health care professionals and suggests the importance of incorporating education on muscular dystrophy into the curricula for health care professionals. A recorded best practice webinar may be an effective, accessible, and convenient way to educate practicing physiotherapists treating people with muscular dystrophy. It is possible that other disciplines may also benefit from additional education in the area. Further research should explore if relevant training in muscular dystrophies maps to content of curricula and investigate the views of people with muscular dystrophy in Ireland on physiotherapy and service requirements.
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Prof Kay Ohlendieck, Department of Biology, Maynooth University
Comparative mass spectrometric profiling of the dystrophin complexome in normal versus pathological muscles with differing degrees of fibre degeneration
Duchenne muscular dystrophy affects almost exclusively boys due to the fact that the defective gene is located on the X-chromosome. Several clinical trials are currently testing non-pharmacological approaches, such as ‘exon-skipping’ therapy. These novel genetic drugs promise to convert severe muscle wasting disorders into milder forms, thereby decisively improving the quality of life for patients suffering from muscular dystrophies. In order to be able to properly evaluate and monitor these new genetic treatments, reliable molecular indicators of disease and therapy status are needed. In relation to establishing new dystrophy-related marker molecules, the proposed research will attempt to identify novel diagnostic, prognostic and therapy-monitoring indicators, as well as elucidate molecular and cellular details of fibre wasting in various dystrophic skeletal muscles. We plan to use the high-throughput screening procedure named proteomics for the identification of novel candidate molecules. The identity of altered muscle proteins is then determined by mass spectrometry. The long-term goal of our research is to establish a reliable biomarker signature for Duchenne muscular dystrophy. This knowledge can be used to evaluate new therapeutic strategies for the elimination of muscle-wasting diseases, such as exon skipping-based gene therapy.
Funding amount: €25,000 (MRCG/HRB Joint Funding Scheme)
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Dr Melissa Bowerman, University of Oxford
Role of the TWEAK/Fn14 pathway in mediating muscle pathology in SMA
This study looked at the role of the TWEAK/Fn14 pathway in mediating muscle pathology in Spinal Muscular Atrophy. The aim was to identify important muscle proteins that may be abnormally present or absent and therefore contribute to muscle dysfunction in SMA. Their ultimate goal was to develop a muscle-specific therapy that could be used alongside a nerve cell-specific treatment to improve disease progression in SMA.
Click here to access Dr. Bowermans published paper from this study.
Funding amount: €50,000 (Including €25,000 from the MRCG/HRB Joint Funding Scheme)
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Prof Thomas Walther, University College Cork
Angiotensin-(1-7) and its analogues for the treatment of muscular dystrophy: mechanisms and development of new treatment strategies
Angiotensin-(1-7) is a small protein which is produced in the body. Previous studies have shown that angiotensin-(1-7) has a range of biological activities in the heart, kidneys, and muscles. In the context of DMD, research has shown that angiotensin-(1-7) can reduce fibrosis and improve muscle strength in a mouse model of DMD. It has been postulated that the molecule exerts these biological functions by binding to a receptor called Mas. However, we identified a second receptor for angiotensin-(1-7) named MrgD. Thus, the receptor mediating the beneficial effects of angiotensin-(1-7) is not known, but is crucially important to determine.
Muscle satellite cells are a class of stem cells, which have the ability to regenerate muscle growth and therefore may have potential importance in DMD therapy. Previous work by the applicants has shown that angiotensin-(1-7) can increase the growth of cardiac and vessel progenitor cells (stem cells) in cell culture and in animal models. Tproposal involves investigating the effects of angiotensin-(1-7) and its receptors on growth of satellite cells isolated from muscles of wild-type or DMD-like mice or animals that are deficient in the receptors Mas, MrgD, or in both, using pharmacological approaches with specific stimulators or known blockers of the Ang-(1-7) receptors. Furthermore, we will test angiotensin-(1-7) and analogues which only stimulate one of the two receptors or both in a mild and a more severe animal model of DMD to test their capacity to improve muscle, breathing, and heart function. This information will provide an understanding of the potential of these proteins in future clinical trials focussed on the treatment of DMD.
Funding amount: €14,515
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Collagen VI Alliance
This international alliance was established in 2015 between AFM-Téléthon, the Muscular Dystrophy Campaign, Muscular Dystrophy Ireland, Cure CMD and the Swiss Foundation for Research on Muscle Disease to fund research into collagen VI deficiencies that will further the development of therapeutic approaches and/or demonstrate a strong translational impact in this research field. Between 2015 and 2022 MDI contributed funds towards this alliance to support some of the following studies:
Project 1 - Professor Volker Straub, Newcastle University
Trial Readiness for Collagen VI Myopathies
Development and testing of novel therapeutics depend critically on availability of appropriate patient populations and standardised mechanisms for monitoring disease state and progression. This included the development of European based registry which will feed directly into the existing North American registry for people with Collagen VI deficiencies. Other aims of this project included: identifying a new cohort of patients through existing large scale sequencing projects; Standardizing outcome measures; neuromuscular imaging; coordinating the collection of clinical data and biomaterials from the patient community.
Project 2 - Nadir Mario Maraldi – Rizzoli Orthopaedic Institute
“Melanocytes as low invasive tool alternative to muscle cells to assess mitochondrial therapies in collagen VI related myopathies”
This study aimed to validate patient melanocyte primary cultures as alternative model to muscle cells for monitoring the response to drug treatments in people with Ullrich congenital muscular dystrophy and Bethlem myopathy.
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Prof Kay Ohlendieck, Department of Biology, Maynooth University
'Biochemical evaluation of the tissue damage-related matricellular protein Periostin as a novel diagnostic, prognostic and therapy monitoring biomarker of dystrophinopathy'
Funding was towards studying the molecular changes in dystrophic muscle tissues with a large-scale biochemical method called proteomics. This application was based on a recent discovery of a new marker of tissue damage in muscular dystrophy. The analysis of an animal model of muscular dystrophy showed a drastically elevated level of an extracellular protein named Periostin. With respect to the potential future usage of Perisotin as a biomarker, its altered expression could be used as an analytical tool for assessing experimental gene therapy.
Amount funded: €25,000
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Dr Honor Nicholl, School of Nursing & Midwifery, Trinity College Dublin
Exploring the Challenges faced by people with Muscular Dystrophy Living Independently
This collaboration between Muscular Dystrophy Ireland (MDI) and Trinity College (Trinity) explored the independent living challenges that people with muscular dystrophy face. This study was funded by the Irish Research Council New Foundations Scheme. An important finding to come out of this research was the lack of information on a range of topics available to participants. Also, over the course of the research it was noted that participants preferred using a range of computer-based assistive technologies to get information.
Amount funded by IRC: €10,000
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Dr Dervla O’Malley, Department of Physiology, University College Cork
To determine if changes in inflammatory muscles contribute to loss of respiratory muscle function in mdx mice.
The aim of this study was to determine if changes in inflammatory status in respiratory muscles contribute to loss of respiratory muscle function in mdx mice. Deterioration of respiratory muscles such as the diaphragm is particularly devastating in DMD with estimates of up to 90% of patients dying from acute respiratory failure. Funding towards this study was in addition to previous MDI funded work that had identified improved diaphragmatic function in mdx mice treated chronically with IL-6 neutralising antibodies under non-hypoxic conditions. Funding for this project was to continue to evaluate the potential of this strategy in a more severe model of respiratory muscle failure relevant to DMD.
Amount funded: €10,000
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Prof Matthew Wood, Department of Physiology, Anatomy and Genetics, University of Oxford University
Personalised medicine for a rare disease: Multiexon skipping targeting the out-of-frame mutation in exons 46 to 51 of the human DMD gene.
This study was an extension of previous work to develop a combination therapy with oligonucleotides in patient derived cells and in a mouse model for DMD with the human dystrophin gene and to combine this approach with the peptide conjugated oligonucleotides that are being developed with the Wellcome Trust Health Innovation Challenge Fund, to develop a high efficiency multiexon skipping treatment which targets out-of-frame mutation in exons 46 to 51 of the human dystrophin gene.
Amount funded: €20,000
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Dr. Aisling Ryan, Cork University Hospital, Prof. Orla Hardiman, and Dr. Stela Lefter, Beaumont Hospital Dublin
Funding to undertake a population-based survey of adult neuromuscular disease in the Republic of Ireland, with particular emphasis on the identification of conditions for which therapeutic options are now available. A secondary aim is to generate specific care programmes for patients with adult-onset neuromuscular conditions in the context of two national referral clinics in Dublin and Cork.
Access the published paper from this study
Amount funded: €20,000
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Dr Jeremy Rhodes, School of Biological Sciences, University of East Anglia
An investigation into the role of double-stranded RNA pattern recognition receptors in myotonic dystrophy.
The aims of this study were: 1. Provide evidence to show that double-stranded RNA pattern recognition receptors are activated by triplet-repeat RNA expression. 2. Identify a link between double-stranded RNA activated pathways and specific molecular characteristics of myotonic dystrophy.
Amount funded: €19,000
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Prof. Richard Costello, Beaumont Hospital
Funding to purchase ten oximeters. These devices can be worn overnight at home and give a simple measure of respiratory function, reducing the need for adults with neuromuscular conditions who require assessment of respiratory function to have an overnight stay in hospital for a sleep study.
Amount funded: €8,000
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Dr. Keith Murphy, University College Dublin
Novel Treatment for Charcot-Marie-Tooth Disease
Charcot Marie Tooth (CMT) disease is a common inherited peripheral neuropathy characterised by sensory and motor deficits resulting from damage to and loss of myelin in peripheral nerves. Although the genetic basis of CMT is well understood, to date this has not led to the development of any drug therapies for the condition. We identified a compound which is effective in repairing myelin in a tissue culture system. This finding raised the possibility that this new drug may be effective in a number of conditions where the symptoms are caused by damage to myelin, including CMT. We will test this idea using trembler-J mice, a strain which has a similar genetic mutation and similar features to type 1A CMT in humans.
The funding provided by Muscular Dystrophy Ireland, went towards the purchase of a rotarod, which allowed us to investigate whether trembler-J mice treated with this drug showed improvement in motor performance, balance and coordination, all of which are affected in these animals. Click here to read Novel Treatment for Charcot-Marie-Tooth Disease.
Amount funded: €4,543
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Prof. Kay Ohlendieck, NUI Maynooth
Establishment of a protein biomarker signature for x-linked muscular dystrophy: Identification of novel integral muscle proteins by mass spectrometry-based proteomics
The main aim of this research proposal is the establishment of a disease-specific protein biomarker signature of x-linked muscular dystrophy, focusing especially on low-abundance and membrane associated proteins. In the long-term, the biochemical and cell biological characterization of disease-specific biomarkers of x-linked muscular dystrophy will help to develop the basis of evidence for decisively improving public health strategies and promote the rationale design of superior diagnostic procedures and therapeutic strategies to counteract fibre wasting in Duchenne muscular dystrophy and related muscle diseases.
The main findings were published in the journal Analytical Biochemistry
Amount funded: €20,000
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Prof Matthew Woods, Department of Physiology, Anatomy and Genetics, University of Oxford University (member of the MDEX Consortium, who ran the exon skipping clinical trials in the UK)
Additional funding for one year to improve the delivery of antisense oligonucleotides to target all muscles including the heart.
Amount funded: €28,666
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Dr. Bryan Lynch, CRC Dublin
Funding to employ a Clinical Research Fellow performing audits of care management and researching bone density in boys with Duchenne muscular dystrophy
Amount funded: €34,500
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Dr. Matthew Wood, University of Oxford
Enhanced Systemic Delivery of Antisense Oligonucleotides for Exon Skipping in Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a severe muscle degenerative disease caused by mutations in the dystrophin gene that prevent correct reading of the genetic code, the result of which is that dystrophin protein is not produced. It was discovered that very short pieces of genetic material – so-called antisense oligonucleotides (AOs) – could alleviate the damaging effects of dystrophin mutations and restore the production of dystrophin protein to affected muscle. This they are able to do by a process called ‘exon skipping’, in which parts of the genetic code affected by the mutation are obscured in such a way that the code can be correctly read once again. AOs therefore have significant potential as medicines for DMD patients. In order to fully exploit this potential it will be essential that the AOs can be effectively delivered to all affected muscles and to the heart. At present this is not possible and even with the use of high AO doses no effective dystrophin correction in the heart has been observed. To address this problem we have been investigating ways to improve the systemic delivery of AOs to all muscles and to the heart with the support of MDI funding and we wish to investigate these methods further and to develop these such that they could be used for clinical application in DMD patients.
Amount funded: €33,752
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Dr. Deniz Yilmazer-Hanke, University College Cork
Contribution of the Inflammatory Reaction in the Muscle in Duchenne Muscular Dystrophy to Depression: Development of New Treatment Strategies
Duchenne muscular dystrophy is characterised by a mutation in the dystrophin gene expressed in muscles, leading to progressive muscle damage and weakness often starting in childhood. Less recognised symptoms in Duchenne muscular dystrophy are however psychological symptoms like anxiety, fatigue, chronic stress and depression occurring during the course of the disease. In general it is assumed that these psychological symptoms are secondary to the muscle disease. However, recent studies indicate that inflammatory reactions in the body themselves can cause depression. Therefore, the damage of muscle fibres inducing an inflammatory reaction within the muscle may contribute to mood disturbances in Duchenne muscular dystrophy. In support of this hypothesis, there is cumulating evidence from several systemic disorders like heart failure or rheumatoid arthritis that antidepressive treatment can improve the course of the disease by reducing depression-associated inflammation. Thus, treatment of the inflammatory component of muscle dystrophies with antidepressants comprises a new therapeutic strategy in Duchenne muscular dystrophy. The aim of the current project is therefore to correlate muscular dystrophy associated changes in muscle with emotional changes in an established Duchenne muscular dystrophy model.
Amount funded: €37,616
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MDEX Consortium, UK
Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: A UK Consortium for Preclinical Optimisation and a Phase I/II Clinical Trial Using Antisense Oligonucleotides.
MDI funding used to:
- Develop the dosing strategy and route of delivery of antisense oligonucleotides (AOs).
- Identify AO sequences for skipping additional exons in order to broaden it out and potentially benefit more people.
- Creating the best AO formulation.
- Determine how to target cardiac muscle as well as skeletal muscle.
Amount funded: £100,000 sterling (Including €49,775 from the MRCG/HRB Joint Funding Scheme towards one part of the project)
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Prof. Kay Ohlendieck, NUI Maynooth
Identification of Novel Biomarkers in Dystrophic Heart and Muscle Fibres Using Comparative Proteomics
To determine which cardiac and muscle proteins are affected in x-linked muscular dystrophy and to identify new biomarkers involved in tissue degeneration. Dystrophinopathies are triggered by primary genetic abnormalities in the dystrophin gene. Deficiency in dystrophin affects skeletal muscle, the heart and the central nervous system to varying degrees. Cardiac involvement in Duchenne patients is represented by the pathoanatomical replacement of cardiac fibres by connective and fatty tissue. Approximately 90% of patients develop a serious impairment of cardiac function during the clinical progression of Duchenne muscular dystrophy. We would like to perform a comparative proteomics screening of both cardiac and skeletal muscle preparations in order to investigate global changes in the protein expression profile of dystrophic fibres. As a model system of x-linked muscular dystrophy, we propose to use total cellular extracts from the heart and leg muscles of the dystrophic mdx mouse. We plan to employ the most advanced variation of comparative proteomics, difference gel electrophoresis with fluorescently tagged protein populations.
Amount funded: €30,000 (Including €15,000 from the MRCG/HRB Joint Funding Scheme)
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Prof. Kay Ohlendieck, NUI Maynooth
Identification of Novel Therapeutic Targets in Dystrophic Muscle Fibres
Amount funded: €22,500