Research funded Autumn 2023/Spring 2024
1. Advancing Genetic Therapies: Engineering Induced Pluripotent Stem Cells to study the Endothelial Pathology in Deficiency of Adenosine Deaminase Type 2 (DADA2)
UCL GOS Institute of Child Health– £ 49,999.51
Prof Despina Eleftheriou (Co-applicants; Prof Paul Brogan, Mr Ying Hong Senior Research fellow)
In 2014 an inherited form of vasculitis was discovered called deficiency of adenosine-deaminase-type-2 (DADA2), caused by mutations in a gene called ADA2.
The treatments currently available for DADA2 are effective in a proportion of patients and efficacy may be lost over time with patients still dying from this disease. To tackle these therapeutic hurdles, the research team is at the forefront of developing potentially curative gene therapy for DADA2. Their approach involves introducing a functional ADA2 gene into a patient’s DNA to replace the faulty one, presenting a pioneering method in vasculitis treatment.
The teams overall research vision is to develop iPSC models of DADA2 to enable testing of new precision genetic therapies for patients with these genetic forms of vasculitis. This approach may also have broad translational potential beyond these rare genetic vasculitides.
Research funded Autumn 2022/Spring 2023
1. Pilot studies to evaluate the feasibility of identifying molecular predictors of refractory and relapsing giant cell arteritis from baseline temporal artery biopsies.
Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds – £49,099.83
Prof Ann Morgan (Co-applicants; Mr Michal Zulcinski, Associate Prof Mark Iles, Prof David Westhead, Dr Kathryn Griffin, Dr Gary Reynolds, Dr James Peters)
This project was developed by rheumatologists, pathologists, and scientists in partnership with individuals with lived experience of GCA. This project will involve the analysis of existing large biological datasets to answer two initial questions:
1. Can relapsing and refractory GCA be predicted at the beginning of the disease by analysing a temporal artery biopsy?
2. Do temporal artery biopsies with no inflammation show a genetic signature that is diagnostic of GCA? So even if the biopsy is negative it can help with diagnosis?
If these pilot studies show positive findings, they will confirm the results using different genetic tests, which have been collected on over 2000 patients with GCA. The next step will be to explore any positive findings further to see if new tests can be developed to improve routine clinical care.
2. Identification of Novel Drug Targets for the Large Vessel Endotype of Giant Cell Arteritis
School of Infection & Immunity College of Medical, Veterinary and Life Sciences, University of Glasgow – £49,985.93
Dr Cecilia Ansalone (Co-applicants; John Cole, Prof Carl Goodyear, Prof Neil Basu)
This application is led by an early career researcher (CA) who is one of the first in the world to have access to and/or experience with single cell sequencing and spatial transcriptomics in vasculitis. She now seeks to apply these technologies in the context of LV-GCA. Before new drugs can be tested, there is an urgent need to find the abnormalities of the immune system in patients with LV-GCA, which can be targeted for drug development to better control blood vessel inflammation and minimise the current dependence on steroids.
3. The role of LRG1 in ANCA-associated vasculitis
Centre for Inflammatory Disease & Imperial College Vasculitis Research Centre, Imperial College London – £49,831.56
Dr Stephen McAdoo (Co-applicants; Dr Maria Prendecki, Dr Robert Maughan)
This project will study the role of a protein called LRG1 in the development of AAV. They believe that this protein may be important in AAV, as it can be found both in the immune cells that cause inflammation in vasculitis, and in the cells lining our blood vessels that are damaged in AAV.
This work will provide important information on the role of LRG1 in AAV and may indicate whether drugs targeting this specific protein should be studied in vasculitis patients. Medications which block LRG1 are already being tested in other diseases and they have been shown to be safe to use in humans. This means it will be easier to rapidly translate the results of this project into developing better treatments for patients with AAV (and potentially other forms of vasculitis and kidney disease) in the future.
4. Feasibility work to collect preliminary data for the project:
Do imagery techniques improve symptoms of anxiety, depression, fatigue & pain in people living with vasculitis?
University of Nottingham – £2,000
Alice Muir, research nurse (Co-applicants; Dr Fiona Pearce, Dr Peter Lanyon, Manpreet Bains, Dr Shanali Perera, Dr Megan Rutter)
They will work on a smaller development project designing their 8-week programme, running it for eight interested volunteers (who are living with vasculitis) and then seeking their feedback about the content and delivery of the programme and whether it is potentially of benefit or not. This would then produce a tangible and hopefully helpful interventional product and gauge the interest in the subject and worth of undertaking more extensive research.
Research Funding Spring 2022
Melody Study
London’s Imperial College – 12 months – £25,000. A jointly funded research study to understand how well third doses of vaccine protect immunocompromised patients against Covid-19. Details here.
Research Funding for Spring and Summer 2021.
“Do people with vasculitis mount an effective response to the Covid-19 vaccination and how long does it last?”
Vasculitis UK has given a grant of £53,364 to a one-year project to be led by Professor Lucy Fairclough, Associate Professor of Immunology at Nottingham University. More details …
Research Funding Autumn 2020/Spring 2021
1. Preclinical studies to develop an RNA targeting novel genetic therapy for STING -associated vasculitis with onset in infancy
UCL Great Ormond Street Hospital – £49,712
Asst. Prof. Despina Eleftheriou (Co-applicants; Prof. Paul Brogan, Dr Haiyan Zhou & Prof. Philip Hawkins)
This 12-month project aims to identify an effective and targeted treatment for SAVI. SAVI (STING-associated vasculitis with onset in infancy) is a rare, devastating and life-threatening genetic form of vasculitis causing severe and persistent inflammation throughout the body, especially in the skin, blood vessels, and lungs.
2. Peptide Immunotherapy in experimental MPO-ANCA vasculitis
Imperial College London – £50,000
Dr Maria Prendecki (Co-applicant: Dr Steve McAdoo )
This 18-month project will investigate how to create tolerance in AAV by studying laboratory rats which develop vasculitis closely resembling disease seen in patients with AAV. In both these rats and many humans with AAV, the component of white blood cells that is recognised as foreign by the immune system is a protein called myeloperoxidase (or MPO). In order to create tolerance to this protein, it is important to know which part of the MPO protein is important in causing disease.
3. Evaluation of CD27+ memory B cell reconstitution following rituximab maintenance therapy in ANCA associated vasculitis as a guide to future dosing
University of Cambridge – £51,562
Dr Rona Smith (Co-applicants; Dr Mark McClure & Prof. David Jayne)
This study will look at 36 patients, with AAV (ANCA associated vasculitis) who have received rituximab. Through a detailed analysis of the returning B cells in the blood stream, they hope to identify a biomarker that reliably predicts an impending flare and may be used in combination with other factors in a relapse prediction model and in future studies to guide the optimal timing of subsequent rituximab doses.
4. Incidence of cardiovascular events and common cancers in ANCA-associated vasculitis and Takayasu’s arteritis in the English population
University of Nottingham – £49,766
Dr Megan Rutter (Co-applicants; Dr Fiona Pearce, Dr Peter Lanyon & Prof. Richard Hubbard)
This research group has identified the number of people in England living with AAV and TAK using routinely collected healthcare data. They will be added to a national rare disease register called NCARDRS. This register will have many benefits, such as allowing better health service planning. Another benefit is that once the people with AAV and TAK are known, the team can use other healthcare data to determine how many of them develop cardiovascular problems such as heart disease, strokes and blood clots. They will also be looking at how often people with AAV or TAK develop 5 common types of cancer: breast, prostate, lung, bowel and bladder. They will then compare the rates of these diseases with people of the same age and sex who do not have AAV or TAK to see whether the rate in AAV and TAK is the same, decreased or increased.
Research Funding Spring/Summer 2020
1. The effect of COVID19 on people with Vasculitis: A Whole Populated Study in England
Dr Fiona Pearce – £32,856,71 – 6 Months
2. SARS Cov-2 Antibody Responses in Immunosuppressed Patients
Dr Rona Smith & Dr Rachel Jones – Contribution of £7,500 – (Total cost of the study is £95,000) – 24 Months
Research Funding Autumn/Winter 2019
1. TARGET Consortium GCAT Biobank – £49,473
Ann Morgan on behalf of Target Consortium (Co-applicants; Dr Sarah Mackie, Dr Charlotte Harden & Prof. Raashid Luqmani)
This three year project brings together the University of Oxford and Leeds Institute of Cardiovascular & Metabolic Medicine. They plan to launch a dedicated biobank for the GCAT (Giant Cell Arteritis Tocilizumab) Registry and to conduct preliminary investigations using these samples. By taking the opportunity to collect and store samples taken from participants in this unique and timely Registry, they will have access to tissue for ethically approved pathogenesis and personalised medicine studies of GCA, making research faster and more cohesive, and bringing greater benefits to patients.
2. Investigation of ANCA-driven Pro-Inflammatory Signalling in Human Monocytes – €49,936
Dr Gareth Brady and Prof. Mark Little
This one year project based at St James’ Hospital will seek to understand how MPO autoantibodies drive the complex, tightly regulated signalling pathways leading to IL-1ß release and to develop inhibitors of its release toprovide an exciting window into the ways antibodies can drive the pathology of autoimmune vasculitis, whilst offering new tools for therapeutic intervention in a specific, targeted manner without the current requirement for global immunosuppression.
3. Utilising a novel data source and national registration to improve patient care, outcomes, and enhance clinical research in Takayasu’s arteritis – £47,996
Dr Fiona Pearce – Dr Matthew Grainge – Prof. Justin Mason – Dr Peter Lanyon
Bringing together the University of Nottingham, Imperial College London and Nottingham University Hospital, this one year project looks at utilising a novel data source and national registration to improve patient care, outcomes, and enhance clinical research in Takayasu’sarteritis, the award will allow them to employ a research manager for 1 year to undertake the research.
Education Funding for Spring 2019
Travel Bursaries have been awarded to six applicants who are attending the 19th International Vasculitis ANCA Workshop, April 7-10th 2019 in Philadelphia, PA
Rare Disease Group Vasculitis Education Day May 2019
Presented by Dr Nina Brown and Dr Fiona Pearce at Salford Royal, sponsored by UKIVAS and supported by Vasculitis UK. Details here
Education Funding for Summer 2018
Vasculitis U.K. and the British Society for Rheumatology are working together to offer 5 “Vasculitis Fellowships”. Successful applicants will experience 3 days of intensive education about all types of vasculitis and will get first hand practical experience working in clinical sessions with a leading expert in vasculitis.
Research Funding Autumn/Winter 2017
- Dr Rachel Jones University of Cambridge. Study entitled ” Tissue Biopsy study in ANCA associated Vasculitis “, £40,750 over 12 months
- Prof Alan Salama University College London, Centre for Nephrology ,Royal Free Hospital, Study entitled ” Investigating the aetiology of Subglottic stenosis in GPA using novel in vitro models “, £42,578 over 24 months
- Dr Louise Oni, University of Liverpool. Study entitled “Working towards a diagnostic test to enable stratification of children with IgA Vasculitis (HSP)”, £21,222.95 over 12 months
- Dr Despina Eleftheriou, Institute of Child Health, University College London. Additional funding of £8560 for the Grant we funded last year entitled “Discovering novel genetic causes of cerebral vasculitides of the young”
- Dr Theresa Page, Imperial College London. Study entitled “Does the calprotectin: RAGE axis contribute to pathogenesis in ANCA associated Vasculitis?” £12,000 over 12 months
Travel Bursaries, March 2017
- Vasculitis UK has funded five professionals to travel to the International Vasculitis ANCA Workshop in Japan.
Research Funding Autumn 2016
- Primary Angiitis of the Central Nervous System.
- Dr Desmond Kidd;The Royal Free London (ucl)
Duration 36 months - Discovering Novel Genetic causes of Cerebral Vasculitides of the young. Prof Paul Brogan and Dr Despina Eleftheriou; Great Ormond Street Hospital.
Commencing October 2016
Research Funding Spring 2015 – Spring 2016
- Improving early diagnosis of Wegeners Granulomatosis ( GPA ) in primary care. Prof Richard Hubbard and Dr Fiona Pearce; University of Nottingham.
Duration 12 months - Management of fatigue in Large Vessel Vasculitis and its overlaps: a feasability study. Dr Sarah Mackie and Dr Emma Harris; University of Leeds.
Duration 12 months - SYK as a novel therapeutic target in systemic ANCA associated vasculitis. Dr Stephen Mackadoo and Dr Ivor Kwame; Imperial College, London.
Duration 12 months - BPSU study on Behcets Syndrome in children and young people in the UK.Dr Clare Pain and Prof Micheal Beresford; University of Liverpool.
Duration 36 months - The informational needs of carers for people diagnosed with ANCA associated vasculitis. Dr Richard Watts and Dr Janice Mooney; University of East Anglia.
Duration: 12 months
Research Funding 2011-2014
- Micro-RNA (Genetic Regulators) – March 2014 – V-UK is part funding a pilot study to be carried out by Dr Nina Brown, of Manchester University Hospital. It is hoped to establish whether “micro-RNA” particles can be found in blood plasma in different levels according to whether the disease was active or in remission and if these particles can also been detected in the urine. If there is found to be a correlation and the particles are also found in urine, it might be the key to a new biomarker for disease activity, thus aiding diagnosis and monitoring of maintenance. In addition it might lead to new drug therapies that would reset the immune system. If the theory proves correct, it would lead to a much larger clinical trial to produce some hard clinical evidence in statistically significant numbers. The majority of the funding for this pilot study is being met by the Manchester Renal Research Fund.
- MYPAN Research Project – Spring 2013 – The Trustees of Vasculitis UK are very pleased to be associated with and part funders of this international trial, which is being led by Dr Paul Brogan of Great Ormond Street Hospital for Children and University College, London. The investigation is into the relative effectiveness of Mycophenolate in treating PAN (Polyarteritis Nodosa) in children. This is a rare condition, especially in children, hence the need to make it an international collaborative study involving other centres throughout Europe. In research terms, you need to have numbers of participants to make the results meaningful and significant. The standard treatment for PAN is with an aggressive immune suppressing drug – Cyclophosphamide. As we all know, although it is very effective, cyclo has numerous undesirable side-effects. For children these are potentially so much more serious. Mycophenolate is also very effective but has fewer serious side-effects. So if Mycophenolate is found to be at least as effective as Cyclophosphamide in controlling PAN in children, they would be spared those side effects, as the known side effects of this drug are relatively mild. The main funding for this research study is being provided by Arthritis UK, but they will only fund the UK part of the project. The other participants in this Europe-wide study are paying their own basic costs, but participation also involves approval by the different regulatory bodies in each country involved. This is a complex and time-consuming process which can be expensive. Vasculitis UK is providing £15k to help in funding this part of the project. If the trial proves to be successful, children suffering from PAN throughout the World may be safely spared the harmful effects of Cyclophosphamide.
- UKIVAS Vasculitis Registry – Vasculitis UK is very proud to be associated with this important research based projects and to be funding it. The Vasculitis Registry is a database of clinical information about vasculitis patients in various centres around the UK. Vasculitis UK support is a five year funding strategy for the new UK and Ireland Vasculitis Registry from March 2013. This is an initiative of the United Kingdom and Ireland Vasculitis Study Group (UKIVAS) and is led by Professor Mark Little, of Trinity College Dublin and Dr Richard Watts, Consultant Rheumatologist at Ipswich. Full information can be found at: Rare.Renal.Org For further information on Trinity College Dublin see: Trinity Health Kidney Centre Membership of UKIVAS is made up of the top UK and Irish experts dealing with the vasculitides. The new Registry will store clinical data from numerous centres all around the UK. This will permit researchers to investigate, for example, the effectiveness of different treatment regimes in a large cohort of patients, especially long term results, as well as the investigation of genetic factors. It will aid the search for more reliable indicators of disease activity, thereby improving diagnosis and will help identify the model for best practice in treatment Until now, in the UK there has been no central database, no co-ordinated system for recording, collecting and sharing this information. Each hospital has its own system, making it very difficult for those involved in clinical research to find out lots of potentially useful information about, for example, how the various types of vasculitis affect different patients, how they respond to different medication, how long before relapse, the side effects of drugs, permanent effects of the vasculitis – and so much more. Now, numerous centres around the UK have agreed to “donate”the data that they have on their vasculitis patients, both past present and future, to this new database in a format that will be accessible. Once there is sufficient data added it will become an incredibly valuable resource for those involved in vasculitis clinical research. As researchers will “buy” the information from the database, it will become self-funding. As the database grows it will become ever more valuable as a research tool. There is no funding for this sort of project from the usual sources of research grants, which demand clear identifiable goals and outcomes. So Vasculitis UK is funding future vasculitis research where there is no other funding available; an investment today for tomorrow’s research.
- Takayasu Arteritis – In the Spring of 2013 Vasculitis UK funded a student elective bursary at the Hammersmith Hospital in London. The project is to update the current Takayasu patient database to provide better and more accurate records on the Takayasu patients who attend the Hammersmith. The information will be for the benefit of Takayasu patients attending the Hammersmith. In addition the data will be used for publication of a paper in a medical journal on the experiences at the Hammersmith and the benefit of early diagnosis in Takayasu Arteritis and the use of new imaging techniques to demonstrate the reversibility of early arterial lesions in those patients.
- Cytomegalovirus – In 2012 the Trust funded research at Birmingham University Hospital into Cytomegalovirus (CMV) and vasculitis, CMV update can be found in the VUK Spring 2016 Newsletter
- Alemtuzumab – In 2011 the Trust part-funded research into the drug Alemtuzumab at Addenbrooke’s Hospital, Cambridge.
Previously funded research
The Trust awarded a postdoctoral fellowship to Dr Neil Holden, Birmingham University Hospital – 2008-2010. This resulted in the publication of the following papers:
- ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process – N J Holden, J M Williams, M D Morgan, et al – Ann Rheum Dis 2011;70:2229-2233. doi:10.1136/ard.2011.153890
- A Dual Role for Diacylglycerol Kinase Generated Phosphatidic Acid in Autoantibody-Induced Neutrophil Exocytosis – Neil J Holden, Caroline O.S Savage, Stephen P Young et al – M O L Med 17 (11-12) 1242 – 1252 , November – December 2011