Understanding and Ameliorating perturbed signalling and pathogenesis in FSHD

Lead Research Organisation: King's College London
Department Name: Randall Div of Cell and Molecular Biophy

Abstract

Diseases can be treated more effectively if the causes/mechanisms underlying the symptoms are known. For muscular dystrophy, the causative defect is changes in genes or DNA that in turn, produce changes to proteins. However, it is generally poorly understood how such defects result in the progressive skeletal muscle weakness and wasting typical of muscular dystrophies.

Every cell in the body contains the same DNA, which is divided into genes, each of which carries the instructions to make a protein(s): the molecules that build, maintain and operate the body. The selection of genes that are expressed (active) in a particular cell type, such as in a muscle fibre, dictate which proteins are made. This gives the cell its special characteristics and functions. For example, muscle genes are not expressed in skin cells, and skin genes are not expressed in muscle cells.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by a change in a particular region of DNA that leads to production of a protein called DUX4, that is not normally present in muscle. DUX4 is a 'transcription factor' meaning that it can control the expression of other genes by binding to their regulatory regions, and so can alter the type of proteins that are made by a cell. Thus the carefully coordinated pattern of gene expression and protein production that enables skeletal muscle to function effectively, is perturbed by the presence of DUX4. This ultimately leads to muscle weakness and wasting.

We have examined gene expression changes during human muscle formation in FSHD cells and used mathematical tools to understand which signalling process are perturbed. We found that pathways that control generation of mitochondria and processes associated with mitochondrial function such as dealing with by-products of metabolism/respiration called reactive oxygen species (oxidative stress) are suppressed. It is well known that FSHD cells are more sensitive to oxidative stress, and a recent clinical trial (clinicaltrials.gov number: NCT01596803) reported that administration of anti-oxidants, improved aspects of muscle function in FSHD patients.

We have found that inhibiting pathways that control generation of mitochondria in healthy human muscle cells makes them appear like FSHD muscle fibres. Conversely augmenting the action of these pathways controlling generation of mitochondria in FSHD muscle cells makes them more like healthy human muscle cells.

This project will investigate how regulation of this pathway controlling generation of mitochondria is perturbed in FSHD and test potential therapeutic strategies to improve its function.

Thus in summary, we will generate tools and models of FSHD that will both further reveal disease mechanisms and also provide a platform for testing potential therapies for FSHD, to underpin possible clinical trials. Better understanding the disease mechanism in FSHD may also highlight other potential therapeutic interventions.

Technical Summary

Facioscapulohumeral muscular dystrophy (FSHD) is the third commonest inherited myopathy, characterised by a descending, often asymmetric, dystrophy with initial involvement of facial and proximal upper limb musculature, and later progression to certain lower limb muscles.

We have examined gene expression changes during muscle formation in human FSHD cells and used mathematical tools to understand which signalling process are perturbed. We found that pathways that control generation of mitochondria and processes associated with mitochondrial function such as dealing with reactive oxygen species are suppressed. It is well known that FSHD cells are more sensitive to oxidative stress, and a recent clinical trial (clinicaltrials.gov number: NCT01596803) reported that administration of anti-oxidants improved aspects of muscle function in FSHD patients.

We have found that inhibiting pathways that control generation of mitochondria in healthy human muscle cells generates myofibres with an atrophic phenotype: characteristic of FSHD muscle fibres. Conversely augmenting the action of these pathways controlling generation of mitochondria in FSHD muscle cells makes them generate myofibres that are larger and indistinguishable from healthy human muscle.

This project will investigate how regulation of this pathway controlling generation of mitochondria is perturbed in FSHD and test potential therapeutic strategies to improve its function.

Main objectives
1. Determine if drugs that increase mitochondrial biogenesis improve the FSHD phenotype in vivo.
2. Validate the mechanism of perturbed mitochondrial biogenesis in FSHD myoblasts.
3. Decipher the action of drugs that improve mitochondrial biogenesis in ameliorating FSHD.
4. Understand the regulation of mitochondrial biogenesis pathways in FSHD.
5: Determine if mitochondrial biogenesis improves DUX4 induced myopathy in vivo.

Planned Impact

This research is directed at understanding pathology of the FSHD, which will inform development/optimisation of treatments. FSHD is autosomal dominant with poorly understood pathophysiology and there is no cure. FSHD presents as an asymmetric, progressive descending skeletal muscle weakness and wasting affecting many muscles that severely affects quality of life: around 30% use a wheelchair. For example, patients can undergo surgery to fix the scapular to the ribcage to stabilize the shoulder, which significantly incapacitates patients for months. FSHD is also associated with sensorineural hearing loss, which can progress to deafness, and a retinal vascular abnormality, which can compromise vision. Lifespan is not attenuated, but means that economic burden lasts many years.

FSHD is the third most common inherited myopathy (prevalence ~1/20,000 http://www.orpha.net). Recent figures indicate that 52 people/year are newly diagnosed with FSHD in the Netherlands, a prevalence of 12/100,000 (1/8333).

Financial Costs: An estimated 70,000 people in the UK in 2010 had a neuromuscular condition, (http://www.muscular-dystrophy.org/assets/0002/0463/Cost_of_Living_with_Muscle_Disease.pdf), creating a considerable financial burden. The Access Economics research published in 2007 put costs of muscular dystrophy for the 3500 Australian patients in 2005 at £258 million a year (http://www.mda.org.au/media/accesslaunch/Gullotta.asp). More recently, calculated annual per-patient costs for neuromuscular disease in the US are $63,693 for ALS, $50,952 for DMD, and $32,236 for DM. Population-wide national costs were $1,023 million (ALS), $787 million (DMD) and $448 million (DM) (Larkindale et al. Muscle Nerve (2014) 49: 431-8). For FSHD, cost per patient year in Germany is 26,240 Euros (Schepelmann et al. J. Neurol. (2010) 257: 15). In addition, > 50% of adult members of the FSHD registry reported that symptoms adversely affected their employment by forced disability, early retirement, or job loss, or that their job had been modified to accommodate physical limitations (http://www.ncbi.nlm.nih.gov/pubmed/22155025).

Quality of Life: 29.6% of FSHD registry members report use of wheelchairs for short or long distances, with 8.3% reporting as "always" using wheelchairs for both. 11.3% of FSHD registry members report use of leg braces at enrolment. The EQ-VAS quality of life score is 0.75 +/- 0.21 (0.81) for FSHD and such a low score associated with increased risk of depression (Winter et al. J. Neurol. (2010) 257(9):1473-81). FSHD registry paper: Moreover, psychological problems occurred in 28.1% of FSHD registry members, with more than one-third reporting having received psychological counselling (Hilbert et al. Contemp. Clin. Trials (2012) 33:302-11).

Direct beneficiaries with immediate impact from the work will include academics, clinicians, and the pharmaceutical industry. Researchers/clinicians will benefit as better understanding pathomechanisms will inform treatment and development of therapies, particularly relevant to progressing from the recent clinical trial involving antioxidants for FSHD that showed improvement in certain parameters (clinicaltrials.gov number: NCT01596803). Pharmaceutical companies and translational researchers will benefit as this will inform planning pre-clinical/clinical trials.

Longer term, patients and carers will benefit from relief of disease burden from better understanding disease pathology and improved therapy. Thus society and the economy benefits from improved treatments, due to reduction in NHS and care costs and both reduced loss of earnings and benefit payments for patients and carers. Biochanin A is available in food supplements and clinically tested, so could be rapidly adopted for FSHD, also encompassing MRC Priorities for Nutrition Research
https://www.mrc.ac.uk/funding/science-areas/population-systems-medicine/mrc-priorities-for-nutrition-research/

Publications

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Engquist EN (2021) The Satellite Cell at 60: The Foundation Years. in Journal of neuromuscular diseases

 
Description Characterising heterogeneity in FSHD - analysis of worldwide patient cohort
Amount $13,200 (USD)
Funding ID FSHDFall2019- 05482908070 
Organisation FSH Society 
Sector Charity/Non Profit
Country United States
Start 03/2020 
End 03/2021
 
Description DUX4 and PAX7 interaction in FSHD pathology- revised 2021
Amount £69,811 (GBP)
Funding ID 19GRO-PG12-0493 
Organisation Muscular Dystrophy UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 03/2022
 
Description Engineering antibody fragments to generate cell-penetrant degrabodies targeting DUX4 for the treatment of facioscapulohumeral muscular dystrophy
Amount £153,890 (GBP)
Organisation UCB Pharma 
Sector Private
Country United Kingdom
Start 02/2022 
End 02/2025
 
Description Four-Year PhD studentship in Basic Science
Amount £111,000 (GBP)
Funding ID 222352/Z/21/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2020 
End 09/2023
 
Description Investigation of metabolic adaptation in FSHD to identify novel pathomechanisms and therapeutics
Amount £74,623 (GBP)
Funding ID 21GRO-PG12-0530-1 
Organisation Muscular Dystrophy UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2022 
End 05/2023
 
Description Therapeutic targeting of mitochondrial dysfunction in FSHD
Amount € 172,865 (EUR)
Funding ID J4435-B 
Organisation Austrian Science Fund (FWF) 
Sector Academic/University
Country Austria
Start 03/2021 
End 03/2024
 
Description Understanding and targeting metabolic dysfunction in FSHD
Amount $55,300 (USD)
Funding ID 3308289076 - FSH Society 
Organisation FSH Society 
Sector Charity/Non Profit
Country United States
Start 04/2021 
End 05/2023
 
Title Isolated zebrafish myofibres to study muscle stem cells in their niche 
Description Described a novel method to isolate zebrafish myofibres, complete with their associated muscle stem cells in situ, to study muscle fibre anatomy and the function of muscle stem cells retained in their niche. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact This novel method to isolate zebrafish myofibres, complete with their associated muscle stem cells in situ, allows study of muscle fibre anatomy and the function of muscle stem cells retained in their niche. This allowed us to examine zebrafish stem cells and discover the important role that the myogenic regulatory factor myogenin plays in stem cell function. 
 
Title Multimodal method for discovering muscle pathologies that may involve muscle stem cell dysfunction 
Description Developed a multimodal method using publicly available data for discovering inherited muscle pathologies that may involve muscle stem cell dysfunction 
Type Of Material Technology assay or reagent 
Year Produced 2022 
Provided To Others? Yes  
Impact Tool enabled inherited muscle pathologies to be identified that are either solely caused by muscle stem cell dysfunction, or where there is a contribution of stem cell dysfunction. Important to know to understand pathomechanisms and when developing/testing new therapies for such diseases. 
 
Title RNA-Sequencing data 
Description RNA-Sequencing data of muscle cells from muscular dystrophy patients and family controls. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact Freely available through GSE for other researchers to re-analyse and use. 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123468
 
Title Transcriptomic data of Muscle and Lymphoblastoid cells from FSHD patients 
Description RNA-Sequencing was performed on primary Muscle and Lymphoblastoid cells from FSHD patients, together with suitable controls lines to provide a dataset of their transcriptomes. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Transcriptomic analysis provided insights into pathomechanisms in the muscular dystrophy FSHD, and is freely available via the GEO database. Results are described in Banerji, C.R.S., Panamarova Macura, M. and Zammit, P.S. (2020). DUX4-expressing immortalised FSHD lymphoblastoid cells express genes elevated in FSHD muscle biopsies, correlating with the early stages of inflammation. Human Molecular Genetics 29, 2285-2299 (doi: 10.1093/hmg/ddaa053). 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153523
 
Description Ameliorating oxidative stress with drugs 
Organisation Pablo de Olavide University
Country Spain 
Sector Academic/University 
PI Contribution Helping a team at Universidad Pablo de Olavide (Sevilla, Spain) to analyse muscle function in a mouse model of mitochondrial disease.
Collaborator Contribution Team at Universidad Pablo de Olavide (Sevilla, Spain) are collaborating on dosing regimes and techniques for delivering drugs to counter mitochondrial disfunction.
Impact This collaboration will help progress projects in both labs and lead to joint ventures.
Start Year 2018
 
Description Biomimetic humanized FSHD muscle disease model 
Organisation University of Applied Sciences Technikum Wien
Country Austria 
Sector Academic/University 
PI Contribution Expertise and cell lines to establish a biomimetic humanized FSHD muscle disease model using a bioreactor-based dynamic 3D culture system.
Collaborator Contribution Access and expertise in using a prototype bioreactor for dynamic 3D culture systems.
Impact We expect the first version of a biomimetic humanized FSHD muscle disease model to be ready by autumn 2021. Expertise of cell biology and muscle disease models from London, combined with biophysics and engineering expertise of University of Applied Sciences Technikum Wien.
Start Year 2020
 
Description Control of myogenic differentiation 
Organisation University of Georgia
Country United States 
Sector Academic/University 
PI Contribution Examining myogenic differentiation and how it is affected by altering signalling pathways known to be perturbed in the muscular dystrophy FSHD.
Collaborator Contribution Supplied a range of human myoblasts engineered to lack key genes involved in myogenic differentiation and fusion.
Impact Project at a preliminary stage at present.
Start Year 2021
 
Description Erasmus exchange 
Organisation University of Mons
Country Belgium 
Sector Academic/University 
PI Contribution Trained an Erasmus student as part of their MSc project.
Collaborator Contribution Organised a student to undertake their project in the lab at King's.
Impact Student obtained a PhD position.
Start Year 2020
 
Description Erasmus sponsored visiting 6 month MSC project Students (x2) 
Organisation University of Applied Sciences Technikum Wien
Country Austria 
Sector Academic/University 
PI Contribution Provided experience and training in muscle cell biology in healthy and muscular dystrophy and redox assessment as part of two Erasmus sponsored 6 month MSC projects for the Tissue Engineering and Regenerative Medicine Masters of the University of Applied Sciences Technikum Wien, Austria.
Collaborator Contribution Provided two highly trained and competent MSc students to undertake projects in the lab to support ongoing work funded by MRC and MDUK.
Impact Projects will very likely contribute data to publications from the Zammit lab.
Start Year 2022
 
Description HIF1A in Muscular dystrophy 
Organisation University of Mons
Country Belgium 
Sector Academic/University 
PI Contribution Exploring the role of HIF1alpha in oxidative stress response in muscular dystrophy using engineered human myoblasts.
Collaborator Contribution Supplying engineered human myoblasts and expertise on analysing HIF1alpha for a complementary project at University of Mons in Belgium. Supplying RNA-Sequencing data.
Impact Cross-fertilisation with a group experienced in analysing HIF1alpha in other systems.
Start Year 2018
 
Description Impact of smoking/vaping on skeletal muscle redox homeostasis 
Organisation University of Reading
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed methods to test mitochondrial function and free radical generation/handling in human myoblasts and immature muscle fibres (as detailed in - Interplay between mitochondrial reactive oxygen species, oxidative stress and hypoxic adaptation in facioscapulohumeral muscular dystrophy: Metabolic stress as potential therapeutic target. Heher P, Ganassi M, Weidinger A, Engquist EN, Pruller J, Nguyen TH, Tassin A, Declèves AE, Mamchaoui K, Banerji CRS, Grillari J, Kozlov AV, Zammit PS. Redox Biol. 2022 Jan 29;51:102251. doi: 10.1016/j.redox.2022.102251.). Using these techniques we are now testing the Impact of smoking/vaping on skeletal muscle redox homeostasis in healthy and diseased muscle cells. The impact of smoking/vaping on skeletal muscle redox homeostasis"
Collaborator Contribution Supplied solute extracts from tobacco smoke and vaping vapour and other reagents to test in our system.
Impact Found that smoking adversely affects skeletal muscle redox homeostasis, which is being prepared for publication.
Start Year 2021
 
Description Measuring oxidative stress 
Organisation Ludwig Boltzmann Society
Department Ludwig Boltzmann Institute for Experimental and Clinical Traumatology
Country Austria 
Sector Academic/University 
PI Contribution We have generated human cell samples to send to Ludwig Boltzmann Institute for Experimental and Clinical Traumatology for analysis of free radicals
Collaborator Contribution Ludwig Boltzmann Institute for Experimental and Clinical Traumatology analyse our samples of human cells for free radical content.
Impact A better understanding of free radical generation in muscular dystrophy will be the outcome, with this joint publication. Publication 10.1016/j.redox.2022.102251 (2022) Interplay between mitochondrial reactive oxygen species, oxidative stress and hypoxic adaptation in facioscapulohumeral muscular dystrophy: Metabolic stress as potential therapeutic target. Redox Biology Jan 29;51:102251
Start Year 2018
 
Description Mechanisms of oxidative/metabolic stress in FSHD 
Organisation Ludwig Boltzmann Society
Department Ludwig Boltzmann Institute for Experimental and Clinical Traumatology
Country Austria 
Sector Academic/University 
PI Contribution Performed a series of Reactive Oxygen Species measurements, respirometric analyses and hypoxia experiments to pinpoint the interplay between hypoxia signalling, ROS and mitochondria in the muscular dystrophy FSHD.
Collaborator Contribution Supply expertise and facilities for examining redox biology to investigate mechanisms of oxidative/metabolic stress in the muscular dystrophy FSHD.
Impact This work has led to the discovery of novel pathomechanisms and potential new class of FSHD therapeutics for FSHD. Combined our expertise in cell biology and FSHD with specialised biochemistry platforms.
Start Year 2020
 
Description Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis 
Organisation Toyohashi Sozo College
Department School of Health Sciences
Country Japan 
Sector Academic/University 
PI Contribution Performing experiments to support the investigation of the role of the mechanosensitive Ion Channel Piezo1 in Myocyte Fusion during Skeletal Myogenesis
Collaborator Contribution Performing main body of work for the investigation of the role of the mechanosensitive Ion Channel Piezo1 in Myocyte Fusion during Skeletal Myogenesis
Impact Fine-Tuning of Piezo1 Expression and Activity Ensures Efficient Myoblast Fusion during Skeletal Myogenesis. Ortuste Quiroga HP, Ganassi M, Yokoyama S, Nakamura K, Yamashita T, Raimbach D, Hagiwara A, Harrington O, Breach-Teji J, Asakura A, Suzuki Y, Tominaga M, Zammit PS, Goto K. Cells. 2022 Jan 24;11(3):393. doi: 10.3390/cells11030393
Start Year 2020
 
Description Muscle biopsy transcriptomic and proteomic analysis 
Organisation Radboud University Nijmegen Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution Will map and analyse gene expression in STIR-positive and STIR-negative muscle biopsies from FSHD patients.
Collaborator Contribution Have obtained muscle biopsies from FSHD patients and will perform proteomic analysis.
Impact RNA-Seq currently being performed by commercial company. Transcriptomics and proteomics.
Start Year 2020
 
Description Muscle regeneration in FSHD 
Organisation University of Rochester
Department University of Rochester Medical Centre
Country United States 
Sector Academic/University 
PI Contribution Performed transcriptomic analysis to measure muscle regeneration in muscular dystrophies including FSHD, DM2 and DMD.
Collaborator Contribution Provide muscle samples labelled with antibodies to assess the amount of regenerating muscle fibres in biopsies from patients with FSHD and DM2.
Impact Banerji, C.R.S., Henderson, D., Tawil, R.N. and Zammit, P.S. (2020). Skeletal muscle regeneration in Facioscapulohumeral muscular dystrophy is correlated with pathological severity. Human Molecular Genetics 29, 2746-2760 (doi.org/10.1093/hmg/ddaa164). Multi-disciplinary - transcriptomics with histopathology.
Start Year 2019
 
Description Pathomechanisms of FSHD 
Organisation University of Minnesota
Country United States 
Sector Academic/University 
PI Contribution Defining the role of a transcription factor, whose regulatory targets are perturbed in the muscular dystrophy FSHD. Investigating how the transcription factor is misregulated to lead to pathology.
Collaborator Contribution Intellectual input and supplying valuable unpublished human muscle cells which have been engineered so that the transcription factor can be controllably over-expressed, together with suitable control lines.
Impact Cells will allow findings made using other techniques/systems to be tested in a highly controllable environment both for confirmation and discovery work.
Start Year 2021
 
Description Performed RNASeq in primary cells from FSHD patients 
Organisation Radboud University Nijmegen Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution Perform and analyse RNA-Sequencing on primary cells from FSHD patients supplied by Radboud University Nijmegen Medical Center, and shared the data. Muscle biopsies from STIR negative and positive muscles and peripheral blood mono nucleated cells from the same FSHD patients were analysesd
Collaborator Contribution Supplied cells from FSHD patients supplied by Radboud University Nijmegen Medical Center and we jointly performed RNA-sequencing.
Impact We have analysed the data and discovered potential new pathomechanisms for FSHD. We have tested FSHD biomarkers on this data set and also derived a new blood biomarker that correlates with the degree of muscle pathology, of importance for monitoring disease progression in FSHD.
Start Year 2019
 
Description RNASeq of primary FSHD cells 
Organisation University of Montpellier
Country France 
Sector Academic/University 
PI Contribution Performed RNASeq in primary muscle cells from FSHD patients supplied by University of Montpellier, and shared the data.
Collaborator Contribution Performed and analysed RNASeq in primary muscle cells from FSHD patients and healthy controls supplied by University of Montpellier, and shared the data.
Impact Data has contributed to a paper under review for Human Molecular Genetics.
Start Year 2019
 
Description Understanding how metabolism is perturbed in muscular dystrophy 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Preparing samples from healthy and diseased human myogenic cells for analysis by the collbaorators.
Collaborator Contribution Advising on experimental design and data interpretation after performing Quantifiable high-resolution NMR spectroscopy at the King's College London (KCL) NMR facility on a Bruker Avance NEO 600 MHz equipped with a TCI Cryoprobe Prodigy and autosampler (https://www.kcl.ac.uk/innovation/research/corefacilities/smallrf/biospectroscopy), under guidance from expert collaborators of the metabolomics facility expert. Data will be analysed using Topsip (Bruker), Matlab and Metaboanalyst providing a quantitative measurement of changes in metabolome, alongside an analysis of potential metabolic pathways affected.
Impact Resulted in successful grant applications to fund this work. Multi-disciplinary: Cell and molecular biology combined with quantifiable high-resolution NMR spectroscopy
Start Year 2021
 
Title Biomarker analysis software 
Description Software that gives a biomarker score for a muscular dystrophy using inputted RNA-Sequencing data. To facilitate consideration of PAX7 target gene repression in the analysis of FSHD transcriptomic data, we provide a simple pipeline for extraction of PAX7 target gene repression, as well as three validated DUX4 target gene expression biomarkers, from normalized gene level expression data. Available as supplementary data from a publication - doi: 10.1093/hmg/ddz043 
Type Of Technology Software 
Year Produced 2019 
Impact A simple pipeline for extraction of PAX7 target gene repression, as well as three validated DUX4 target gene expression biomarkers, from normalized gene level expression data 
URL https://academic.oup.com/hmg/article/28/13/2224/5376488#supplementary-data
 
Title Image analysis 
Description Image analysis software to determine the degree of myogenic differentiation in a culture of cells. 
Type Of Technology Software 
Year Produced 2019 
Impact Allows myogenic differentiation to be quantified in a high throughput way. 
 
Description 9th TERMIS Winterschool 2022 "A Workshop Series on Current Hot Topics in Regenerative Medicine" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Co-chaired and spoke at a session on skeletal muscle at the 9th TERMIS Winterschool 2022 "A Workshop Series on Current Hot Topics in Regenerative Medicine" to an audience of mainly post-graduate students and professionals to educate on skeletal muscle, explain our work funded by MRC and MDUK, and foster collaborations. Other members of the group (2 postdocs) also presented.
Year(s) Of Engagement Activity 2022
URL https://trauma.lbg.ac.at/news/neuer-termin-die-termis-winterschool-2022/?lang=en
 
Description Amis FSH Site Visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Board and members of charity AMIS FSH performed a site visit to King's College London on 20/2/2020. This involved visits to the lab and then talks/discussions with Zammit group members explaining facioscapulohumeral muscular dystrophy and our research activity in lay terms. This better informed the participants about the disorder and research approaches, that will also be fed back to other charity members. Outcomes are dissemination of information and potential for research funding.
Year(s) Of Engagement Activity 2020
URL http://www.amisfsh.fr
 
Description FSHD UK 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact FSHD UK is a patient-lead advocacy group of which I am a member, with the overarching aim of organising patients to take part in clinical trials, disseminating information and, ultimately, contributing to finding a cure for FSHD. We have liaised with Pharma about bringing a US-based clinical trial to the UK.
Year(s) Of Engagement Activity 2021
 
Description Friends of FSH Research website update on research 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact An update to funders, patients, stakeholders and their supporters hosted on the charity Friends of FSH Research website. Lay update on research conducted as part of an MRC grant that was subsequently funded by a fellowship and Friends of FSH Research.
Year(s) Of Engagement Activity 2022
URL https://www.fshfriends.org/blog/progress-update-novel-therapeutics-fshd-mitochondria-targeted-antiox...
 
Description MDUK Muscles Matter online seminar series 2021 Facioscapulohumeral muscular dystrophy 
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 Gave a lay talk on the background to Facioscapulohumeral muscular dystrophy for the MDUK Muscles Matter online seminar series 2021 attended by patients, care-givers, supporters and stakeholders which helped people understand the disorder better and then participated in a panel discussion to answer questions from the audience.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=nsV2YK7II38&list=PLryAKPouaA__KVZa4pSVxYieRWYi57p97&index=6
 
Description Patient Group Workshop 
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 FSHD Information Day - Muscular Dystrophy UK
Talk: - title - What causes FSHD and how can we treat it?
York Racecourse, Knavesmire Road, York YO23 1EX
23/11/19
Talk explaining FSHD and current research to a lay and specialist audience. Many comments about this being the first time that they had actually understood the causes of their disease. Pdf of the talk was requested for dissemination to patents/carers/supporters.
Year(s) Of Engagement Activity 2019
URL https://www.musculardystrophyuk.org/wp-content/uploads/2019/11/Information-Day-November-2019-full-pr...
 
Description School Visit to King's College London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Approximately 80 male and female year 7 pupils, with 6/7 school staff undertake histological staining and examining tissue sections under light microscopes. They were highly engaged with the topic, generating an active discussion and expressions of interest in STEM subjects. Useful experience for Zammit lab members who reported it an enlightening and rewarding activity.
Year(s) Of Engagement Activity 2018,2019,2020
 
Description Site visit by executives of Charity FSHD Soc 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact FSHD Soc charity site visit by Chief Science Officer and Chief Executive Officer of one of the major funders in FSHD research, to discuss our research activity, funding opportunities and further engagement by the Zammit group in charity events.
Year(s) Of Engagement Activity 2020
URL https://www.fshdsociety.org