SRUK is the only UK charity dedicated to funding research into Scleroderma and Raynaud’s. By funding novel scientific research projects, we aim to improve the lives of people living with Scleroderma and Raynaud’s.
Our Research Strategy underpins all of the work funded by SRUK, and was developed to reflect the priorities of the patient and research communities. This resulted in the creation of four research themes, which are explained further in our research strategy:
- Precision medicine
- Early detection and diagnosis
- Quality of life
- Causes of Scleroderma and Raynaud’s
We fund high quality, high impact work across our research themes which will advance the options of diagnosis, care, and treatment available to those living with Scleroderma and Raynaud’s. As a member of the Association of Medical Research Charities (AMRC), SRUK are guided to ensure we are funding the best research, and researchers within the sector. This is made possible through the support of our peer reviewers, and our expert Research Committee.
Read more about about our previously funded research projects below:
2024 SRUK Grant Call
Project Title: Deciphering Seronegative Systemic Sclerosis
- Lead Investigator: Dr Sarah Tansley
- Lead Institution: University of Bath
- Funding Amount: £74,995
- Research Strategy Areas: Precision Medicine, Early Detection & Diagnosis
Summary: Most patients with Systemic Sclerosis (SSc) have detectable autoantibodies in their blood, which help predict disease outcomes. However, around 20% of patients are “seronegative,” meaning they lack these autoantibodies. Seronegative patients often experience worse skin disease and face higher risks of mortality, yet their condition is poorly understood.
This project aims to uncover rare or previously undiscovered autoantibodies in seronegative patients to improve understanding of their disease. Researchers will analyse blood samples from over 250 seronegative patients using advanced techniques to identify these hidden autoantibodies. The findings could refine disease predictions, improve patient care, and enable personalised treatment approaches.
Impact: By identifying new autoantibodies, this research could lead to better tools for predicting disease progression and tailoring treatments for seronegative patients. Ultimately, it aims to improve outcomes and quality of life for individuals living with Systemic Sclerosis.
Project Title: Studying the Ability of Immunosuppression and Anti-Fibrotic Therapy to Modulate Cardiac MRI-Detected Myocardial Abnormalities in Systemic Sclerosis
- Lead Investigator: Professor Maya Buch
- Lead Institution: University of Manchester
- Funding Amount: £73,188
- Research Strategy Areas: Precision Medicine, Early Detection & Diagnosis
Summary: Systemic sclerosis (SSc) is a complex autoimmune disease that can affect multiple organs, including the heart. Heart involvement (HI) is a major contributor to SSc-related deaths, yet it often goes undetected until significant damage has occurred. Cardiac MRI (CMR) is a powerful tool that can identify heart muscle inflammation and fibrosis, even in patients without obvious symptoms. This project aims to evaluate whether commonly used treatments for SSc—immunosuppressive and anti-fibrotic therapies—can improve heart abnormalities detected by CMR.
The study will involve patients requiring treatment escalation, who will undergo CMR scans before and after six months of therapy to assess changes in heart function and tissue abnormalities. A control group of patients not requiring treatment escalation will also be included. By monitoring these changes, the research seeks to advance understanding of heart involvement in SSc and provide evidence for precision therapies.
Impact: This research could lead to earlier detection of heart complications in SSc patients and provide critical evidence for tailoring treatments to improve cardiac health in SSc.
The 2023 SRUK/World Scleroderma Foundation Grant Call
Project Title: Deep-Learning Derived Chest CT Biomarkers as Prognostic Predictors in SSc-ILD
- Lead Investigator: Professor Elisabetta Renzoni
- Lead Institution: Royal Brompton and Harefield Hospitals/Imperial College London
- Funding Amount: £149,951.60 (50% co-funded by the World Scleroderma Foundation)
- Research Strategy Areas: Precision Medicine, Early Detection & Diagnosis
Summary: Interstitial lung disease (ILD) is a serious complication of systemic sclerosis (SSc), affecting over half of patients and leading to progressive lung fibrosis in many cases. This project aims to use advanced deep-learning techniques to analyse chest CT scans and identify biomarkers that can predict disease progression. By studying archived CT scans from 1,000 patients across the UK and Europe, researchers will assess lung abnormalities and develop tools to differentiate between patients at high risk of ILD progression who need immediate treatment, and those at low risk, who may not require intervention.
The study will focus on three key algorithms:
- Total airway volume to predict ILD progression.
- Total vessel volume to assess the risk of pulmonary hypertension.
- Total fibrosis extent to evaluate survival and disease progression compared to traditional lung function measures.
The findings will inform a larger global study, enhancing prognostic accuracy and treatment strategies for SSc-ILD patients.
Impact: This research could revolutionise how ILD in systemic sclerosis is diagnosed and managed, enabling earlier and more accurate predictions of disease progression. By identifying high-risk patients, it aims to improve treatment decisions and outcomes, ultimately enhancing quality of life for those living with SSc.
2022 Research Funding
Project Title: PASTIES – Patient Stratification and Individualised Treatment in Systemic Sclerosis
- Lead Investigator: Dr Clare Pain
- Lead Institution: University of Liverpool
- Funding Amount: £99,979 (50% co-funded by Alder Hey Charity)
- Research Strategy Areas: Precision Medicine
Summary: Systemic sclerosis (SSc) is a complex autoimmune disease, and juvenile cases have been largely overlooked in previous research. Current treatment approaches rely on trial-and-error methods, which can lead to poor outcomes. This project focuses on understanding the molecular mechanisms underlying juvenile SSc, including genetic, epigenetic, and transcriptional changes, to identify biomarkers for improved diagnosis, prognosis, and therapeutic targets.
The study integrates clinical, demographic, and laboratory data, including auto-antibody status, to correlate with observed molecular changes. The findings aim to enhance patient stratification, enabling more targeted and effective treatment approaches. Future studies will involve larger patient cohorts to validate the findings and develop a patient stratification tool.
Impact: This research has the potential to transform the treatment of juvenile SSc by enabling personalised medicine approaches. By identifying specific biomarkers and molecular mechanisms, it could lead to more effective treatments, improved patient outcomes, and reduced long-term complications associated with the condition.
SRUK & World Scleroderma Foundation Grant Call 2021: ‘Stratified Medicines of the Future’
Project Title: Advanced in vitro test systems with integrated multi-“OMICS” to define pathway activation and treatment response scores for patient stratification towards personalised medicine in systemic sclerosis.
- Lead Investigator: Professor Jörg Distler
- Lead Institution: University Hospital of Dusseldorf
- Amount Funded: £97,600 (50% co-funded by the World Scleroderma Foundation)
- Research Strategy Areas: Precision Medicine
Summary: Systemic sclerosis (SSc) presents significant variability in molecular changes, clinical progression, and therapy responses among patients, making effective patient stratification and treatment development challenging. This project aimed to develop a novel toolset for molecular stratification of SSc patients, enabling personalised therapy selection and early assessment of treatment responses to prevent prolonged use of ineffective treatments.
The study utilised precision-cut skin slices from patients and advanced molecular screening techniques, combined with machine learning and biostatistical analyses, to define SSc-specific transcriptomic signatures and generate molecular response scores (MRS) for evaluating therapy efficacy. Two transcriptomic signatures were established, and molecular treatment response signatures were created to predict individual patient responses based on their baseline skin transcriptomic profiles.
Impact: The developed molecular signatures facilitate rapid evaluation of treatment effectiveness in clinical practice, potentially minimising irreversible tissue damage and improving patient outcomes. These tools could also allow better stratification in clinical trials, helping to optimise therapy selection for SSc patients.
2021 Research Funding
Project Title: Prognostic Uncertainty in SSc-ILD: The Use of Novel Deep-Learning Techniques to Enhance Prognostic Evaluation
- Lead Investigator: Professor Elisabetta Renzoni
- Lead Institution: Royal Brompton and Harefield Hospitals/Imperial College London
- Amount Funded: £33,257.14
- Research Strategy Areas: Precision Medicine, Quality of Life
Summary: This project focused on systemic sclerosis-associated interstitial lung disease (SSc-ILD), aiming to improve prognostic evaluation for patients diagnosed with this condition. The study utilised a deep-learning tool called SOFIA (Systematic Objective Fibrotic Imaging Analysis Algorithm) to analyse lung scans and identify specific patterns, such as usual interstitial pneumonia (UIP), associated with disease severity.
The findings revealed that the detection of UIP by SOFIA indicates a higher risk of serious symptoms and greater disease progression. This enables clinicians to identify patients who may require more urgent care and tailored treatment strategies.
Impact: The advancement offered by SOFIA improves the accuracy and consistency of prognostic evaluations, leading to better management of SSc-ILD and more informed treatment decisions for patients and healthcare providers. The project also led to a follow-on study to further enhance prognostic tools.
Publications: “Deep-learning CT imaging algorithm to detect usual interstitial pneumonia pattern in patients with systemic sclerosis-associated interstitial lung disease: association with disease progression and survival.” Available here.
SRUK-MRC Clinical Research Training Fellowship
Project Title: Defining Pathogenic B Cell Regulation and Its Role in Scleroderma-Associated Interstitial Lung Disease
- Lead Investigator: Dr Nina Goldman
- Lead Institution: Royal Free Hospital/University College London
- Amount Funded: £272,802.00 (50% co-funded by the Medical Research Council)
- Research Strategy Areas: Precision Medicine (Effective Drug Treatments)
Summary: This project investigates systemic sclerosis-associated interstitial lung disease (SSc-ILD), a severe autoimmune condition characterised by lung fibrosis and high mortality rates. The study focuses on the role of B cells and autoantibodies in disease progression and treatment responsiveness. The goal is to identify biomarkers that predict responsiveness to biologic therapies (rituximab and tocilizumab) and define the properties and functions of B cells, their antibody signatures, and their impact on lung fibrosis.
The methodology includes retrospective clinical assessments of SSc cohorts, autoantibody profiling, single B cell transcriptome and antibody repertoire analyses, and single-cell RNA sequencing (scRNA-seq) to characterise repopulating B cells post-treatment. Techniques established in rheumatoid arthritis and multiple sclerosis are applied to study B cell subsets and their relevance to SSc.
Impact: The study aims to develop predictive models for disease outcomes, particularly lung function, and understand how B cells interact with fibroblasts in driving lung fibrosis. Findings may also have implications for other autoimmune or fibrotic lung diseases.
Publications:
- Beesley C (2023) – “Dysregulated B cell function and disease pathogenesis in systemic sclerosis” (Frontiers in Immunology). Available here.
- Goldman N (2023) – “Rituximab and tocilizumab and their effect on lung disease progression in scleroderma: a retrospective cohort study” (Rheumatology). Available here.
SRUK “Quality of Life in Systemic Sclerosis and Raynaud’s” Grant Call
Project Title: Scleroderma in the Mouth: Improving Pathways to Care
- Lead Investigator: Professor Liz Walker
- Lead Institution: University of Hull
- Amount Funded: £36,769.42
- Research Strategy Areas: Quality of Life
Summary: This project aimed to improve dental care and quality of life for individuals living with Scleroderma by addressing the often overlooked oral and dental problems associated with the condition. The study highlighted significant gaps in communication between patients and clinicians regarding oral health, as well as the psychosocial impact of oral and dental disease manifestations.
Key findings revealed that almost all participants with Scleroderma experienced various oral and dental issues, yet few surveyed rheumatologists routinely discussed oral health with patients. Early intervention was emphasised as critical, with recommendations for rheumatologists and nurse specialists to routinely inquire about oral health during diagnosis and ongoing care.
The project also identified gaps in information provision and referral processes, with both dentists and rheumatologists expressing a lack of confidence in managing oral and dental issues related to Scleroderma. Resources were created to support patients and clinicians in identifying, treating, and managing these problems.
Impact: The study led to the development of resources aimed at improving awareness and confidence among clinicians, while providing patients with a better understanding of the oral and dental problems associated with Scleroderma, thus enhancing patient care.
Publications:
- Mills, T.J., Price, E., Aggarwal, V., Del Galdo, F., Walker, L. (2023). “Clinicians and Patient Experiences of Managing and Living with Oral and Dental Manifestations of Scleroderma: A Scoping Review.” Journal of Scleroderma and Related Disorders. Available here.
- Mills, T.J., Price, E., Aggarwal, V., Del Galdo, F., Walker, L. (2024). “Oral health and dental care challenges in scleroderma – perspectives of dentists, rheumatologists, and patients.” Rheumatology Advances in Practice. Available here.
Project Title: Self-Assessment of Skin Thickness in Systemic Sclerosis – Improving Quality of Life and Value of Telemedicine for Scleroderma by Empowering Patients
- Lead Investigator: Professor Christopher Denton
- Co-Investigators: Dr Julia Spierings (Royal Free Hospital), Dr Voon Ong (Royal Free Hospital), Professor Ariane Herrick (Royal Hospital Manchester), Professor Francesco Del Galdo (University of Leeds), Dr John Pauling (Royal National Hospital for Rheumatic Diseases)
- Lead Institution: Royal Free Hospital
- Amount Funded: £19,000
- Research Strategy Area: Quality of Life
Summary: This project aimed to empower patients with systemic sclerosis (SSc) by developing and evaluating the PASTUL (Patient self-Assessment of Skin Thickness in Upper Limb) questionnaire. Skin thickening is a key indicator of disease progression and treatment response in SSc. The study assessed the reliability of the PASTUL tool and explored its impact on quality of life. A cohort of 196 patients across four UK centres participated, completing the PASTUL questionnaire alongside clinician-assessed skin scores and quality-of-life measures. The findings demonstrated that the PASTUL tool is a reliable method for self-assessment, correlating strongly with clinical evaluations.
Impact/Outputs:
- The PASTUL questionnaire provides a valuable tool for patients to self-assess skin thickness, enabling better disease monitoring and management.
- Higher PASTUL scores were linked to poorer quality of life and reduced daily functioning, emphasising the importance of addressing skin severity in SSc care.
- The project contributes to advancing telemedicine and patient empowerment in systemic sclerosis management.
SRUK/World Scleroderma Foundation Joint Grant Call 2020: ‘Outcome Measures in Systemic Sclerosis’
Project Title: Validation of clinically and patient meaningful score values of ACR CRISS for diffuse cutaneous SSc.
- Lead Investigator: Professor Francesco Del Galdo
- Co-Investigators: Dr Dan Furst (University of California), Dr Dinesh Khanna (University of Michigan)
- Lead Institution: University of Leeds/Chapel Allerton Hospital
- Amount Funded: £48,958.91 (50% co-funded by WSF)
- Research Strategy Areas: Precision Medicine (Outcome Measures)
Summary: This project focused on improving outcome measurements for diffuse cutaneous systemic sclerosis (dcSSc), a severe form of systemic sclerosis that significantly impacts patients’ lives. The study aimed to validate the Ranked Composite Important Difference (RCID) score, a new objective measure designed to assess treatment efficacy in clinical trials. Collaborating with rheumatologists and patients across five continents, the project evaluated the RCID score’s ability to reliably determine whether patients worsened or improved during trials. The RCID score incorporates key metrics such as lung function, skin thickness, and organ involvement, aligning with the ACR CRISS framework.
Impact/Outputs:
- The RCID score provides a robust and meaningful tool for assessing treatment outcomes in dcSSc, complementing existing measures like ACR CRISS.
- High agreement between patient and clinician rankings ensures the RCID score reflects both clinical and patient priorities.
- Findings empower clinicians and researchers to better assess treatment effectiveness, ultimately improving patient outcomes and advancing drug development for dcSSc.
Publications:
- Del Galdo F, Huang S, Bissell LA, et al. Validation of Ranked Composite Important Difference (RCID) Score in Early Diffuse Cutaneous Systemic Sclerosis. Annals of the Rheumatic Diseases. 2023. Available here.
Project Title: The CRISTAL Index: Developing a combined response index for scleroderma trials assessing limited cutaneous systemic sclerosis.
- Lead Investigator: Dr Dinesh Khanna
- Co-Investigators: Dr Alain Lescoat (University Hospital of Rennes)
- Lead Institution: University of Michigan
- Amount Funded: £50,000 (50% co-funded by WSF)
- Research Strategy Area: Precision Medicine (Outcome Measures)
Summary: This project addressed the need for effective outcome measures to assess limited cutaneous systemic sclerosis (lcSSc), a significant subgroup of systemic sclerosis (SSc). Despite being considered a milder form, lcSSc can lead to substantial organ complications and decreased quality of life. The study aimed to develop the CRISTAL Index (Combined Response Index for Scleroderma Trials Assessing Limited Cutaneous Systemic Sclerosis), a standardised tool for evaluating disease progression and treatment efficacy. Through focus groups, literature reviews, and expert consensus, the project identified relevant outcome measures and domains to support future clinical trials.
Impact/Outputs:
- The CRISTAL Index provides a robust framework for assessing lcSSc in clinical trials, facilitating drug development and improving patient outcomes.
- Focus groups identified 15 bothersome domains from the patient perspective, including gastrointestinal involvement, Raynaud’s phenomenon, and musculoskeletal symptoms.
- A consensus endorsed 18 outcome measures for future longitudinal studies, ensuring relevance to both patients and clinicians.
- The project sets the stage for international observational studies to validate the CRISTAL Index and refine its application in clinical research.
- This project therefore provides a critical step forward in improving clinical trial design and treatment evaluation for patients with limited cutaneous systemic sclerosis.
Publications:
- Lescoat A, Murphy SL, Roofeh D, et al. Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes. J Scleroderma Relat Disord. 2021. Available here.
- Lescoat A, Sandler RD, Zimmermann F, et al. Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: an international collaborative scoping review. Rheumatology (Oxford). 2022. Available here.
- Lescoat A, Murphy SL, Chen YT, et al. Symptom experience of limited cutaneous systemic sclerosis from the patients’ perspective: A qualitative study. Semin Arthritis Rheum. 2022. Available here.
SRUK/Engineering and Physical Sciences Research Council (EPSRC) Hackathon for a Diagnostic Tool
‘The SRUK/EPSRC Hackathon’ was a three-day event held in February 2020 which brought together clinicians, bioengineers, data scientists and bioscientists from University and industry to produce ideas for new devices which could easily and objectively measure the skin to diagnose and monitor the effects of scleroderma. The modified Rodnan Skin Score (mRSS), the current method of measuring the skin, requires extensive training and due to the subjective nature of the test, can result in variability of results between clinicians.
Four of the projects which were developed during the Hackathon event submitted applications for funding, totalling £418,000, of which two were funded. This call was carried out in partnership with the Engineering and Physical Sciences Research Council (EPSRC) who assisted in the delivery of the Sandpit event and co-funded one of the awarded projects.
Project Title: Objective Assessment of Scleroderma Skin Tissues (OASIS)
- Lead Investigator: Dr Peter Worsley
- Co-Investigators: Dr David Childs (University of Glasgow), Dr Ashleigh Boyd (University College London), Dr Francesco Del Galdo (University of Leeds), Dr Rodney Gush (Moor Instruments Ltd)
- Lead Institution: University of Southampton
- Amount Funded: £117,939.17 (SRUK funded)
- Research Strategy Areas: Early Detection and Diagnosis, Precision Medicine
Summary:
The OASIS project aimed to develop reliable, non-invasive tools for assessing skin health in systemic sclerosis (SSc). Current methods, such as the modified Rodnan Scale, are invasive and painful, prompting the need for alternatives. The study explored tools from other fields to measure skin properties like water loss, hydration, and stiffness. These tools were tested in a lab with healthy volunteers and later applied in clinical settings with SSc patients. The project demonstrated the ability of these tools to distinguish between thick and thin skin areas, providing insights into skin stiffness and hydration levels.
Impact/Outputs:
- The MyoTonePRO device showed high correlation with the modified Rodnan Scale, offering a reliable, pain-free alternative for assessing skin stiffness.
- Non-invasive sampling revealed local inflammation markers in some patients, enhancing understanding of disease progression.
- Short-term plans included comparing measurements with optical coherence tomography (OCT) for further insights into skin changes.
- Long-term goals involve developing home monitoring devices for patients to track skin changes, enabling timely clinical interventions.
- This project therefore provided a step forward in improving skin assessment methods for systemic sclerosis – offering evidence to support the use of reliable, non-invasive tools that reduce patient burden and increase clinical accuracy.
Further Funding:
- Project Title: ‘Temperature modulation of skin tolerance to applied mechanical loading and shear’.
-
Researchers: Dr Davide Filingeri & Professor Peter Worsley
-
Research funder: Medical Research Council
Project Title: A bio-inspired solution for a window into the culprit of disease (SCIDEX)
- Lead Investigator: Dr Benjamin Almquist
- Co-Investigators: Dr Claire Higgins (Imperial College London), Professor Maya Butch (University of Manchester), Dr Francesco Del Galdo (University of Leeds)
- Institution: Imperial College London
- Amount Funded: £119,998.30 (Co-funded by the EPSRC)
- Research Strategy Areas: Early Detection and Diagnosis, Precision Medicine
Summary: The SCIDEX project focused on developing a minimally invasive microneedle-based device for sampling interstitial fluid (ISF) from systemic sclerosis (SSc) patients. The goal was to identify biomarkers that could improve disease staging, monitoring, and management. The study involved mechanical skin characterisation, microneedle development, hydrogel optimisation, and proteomic analysis of ISF. Key findings included distinct proteomic changes in early-stage SSc, such as upregulation of inflammatory markers and downregulation of extracellular matrix proteins.
Impact/Outputs:
- Analysis of ISF provided a promising method for staging and monitoring SSc progression, enabling earlier intervention.
- Development of a microneedle-based ISF sampling device for SSc patients.
- Identification of proteomic changes identified in ISF fluid offers strategies for enhancing disease staging and monitoring.
- This project therefore aids the development of innovative tools for disease monitoring and biomarker identification, which brings potential for earlier intervention and improved patient outcomes.