Grant Call Summary

In 2018’s grant call from SRUK there were 9 applications, with requests for funding reaching almost £500,000. From these, following peer review from the wider Raynaud’s and scleroderma research community, 4 applications were selected and funded by the Scientific Advisory Committee. 

Project Title: Elicitation of expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, juvenile localised scleroderma (JLS)

• Lead Investigator: Dr Clare Pain
• Co-Investigators: Dr Despina Eleftheriou, Professor Thomas Jaki, Professor Athimalaipet Ramanan, Professor Michael Beresford
• Institution: Alder Hey Children’s NHS Foundation
• Amount Funded: £13,610.00
• Research Strategy Area: Effective Drug Treatments

Project summary:
JLS is a rare condition, typically affecting 221 children in the UK, with very serious implications for the child affected. Methotrexate is currently the only treatment available, although it is typically used in chemotherapy for treatment of cancer, and acts by suppressing the immune system, meaning it has toxic side effects.

Mycophenolate mofetil is an alternative treatment which works in a similar manner. There is currently some evidence to suggest that mycophenolate mofetil can have the same efficacy as methotrexate in treating JLS, but with reduced toxic side effects.

As the condition is so rare, a traditional clinical trial to test the effects of these two drugs against each other will not be feasible as these require larger numbers of patients. In order to accelerate progress and bring a potentially beneficial treatment to children with JLS sooner, a critical expert meeting and panel to design a novel clinical trial that does not rely on large numbers is essential. A two-phase plan was set out, with SRUK funding supporting the first phase.

1. To hold an international expert consensus meeting to establish prior opinion and knowledge that is critical to informing a future clinical trial and how it is designed.

2. The undertaking of the proposed clinical trial

This meeting will create consensus and consolidate expert opinion, thus forming the basis of a trial that will maximise and benefit a small patient group within a shorter period of time.

Project Title: Preclinical pathological signs of systemic sclerosis in Raynaud’s patients at risk of scleroderma

• Lead Investigator: Dr Francesco Del Galdo
• Co-Investigators: Dr Natalia Riobo-Del Galdo, Dr Yasser El-Sherbiny
• Institution: University of Leeds
• Amount Funded: £28,312.00
• Research Strategy Area: Early Detection and Diagnosis

Project summary:
Thousands of patients are diagnosed every year with secondary Raynaud's, due to the presence of scleroderma specific anti-nuclear antibodies (ANA) or the presence of specific capillaroscopy changes. Either of these represent a risk factor for developing scleroderma. This project seeks to explore whether, within patients who have been diagnosed as 'at risk' there are already signs of change within the immune system, or other systems in the body that are linked to disease activity before the clinical onset of scleroderma. Over 3 years blood and skin samples will be collected at 6 month intervals and analysed to determine the presence of biomarkers. This study takes a novel approach by analysing a persons biomarkers before the onset of scleroderma to identify the mechanisms responsible for the onset of scleroderma in at risk patients.

Project Title: Using microneedle patches to administer novel anti-fibrotic peptides in order to treat scleroderma

• Lead Researcher: Dr Richard Stratton
• Institution: Royal Free London NHS Foundation Trust Hospital
• Amount Funded: £77,008.75
• Research Strategy Area: Effective Drug Treatments

Project summary:
Skin fibrosis can cause limited mobility and dexterity due to skin thickening, making it a symptom of scleroderma which has a significant impact on a persons quality of life. This project connects to a previously awarded SRUK grant which investigated the potential of certain scleroderma biomarkers to be a target for disease therapy. It was discovered that bacteria derived peptide therapeutics (developed by Riptide Bioscience) could prevent the growth of macrophages, which play an active role in the development of fibrosis.  In this next phase of research, Dr Stratton seeks to establish whether the peptide therapeutics can be administered directly to the skin via polymer microneedles, and the efficacy of doing this, through trials on mouse models of skin fibrosis and biopsy material from patients. This method of delivery is expected to minimise side effects as the treatment and has the potential to revolutionise treatment for both localised and systemic scleroderma.  

Project Title: Profiling of subpopulations of monocytes and monocyte-derived cells in scleroderma to identify targets for biomarker, patient stratification and therapy

• Lead Investigator: Dr Angela Tam
• Co-Investigators: Dr Voon-Ong, Professor David Abrahams
• Institution: Royal Free London NHS Foundation Trust Hospital
• Amount Funded: £40,000
• Research Strategy Area: Effective Drug Treatments

Project summary:
Chronic inflammation and excessive scarring in scleroderma is caused in part by the migration of monocytes, a type of white blood cells into tissues via the blood stream. The aim of this study was to characterise subsets of the white blood cells (monocyte / macrophage), and the specific function of each subtype in people with scleroderma, to inform future work into potential therapeutics or treatments in this area.