Four New Research Grants: Our investment in research this year

Date: Fri 28th December 2018

At Scleroderma & Raynaud's UK, we are committed to investing in Scleroderma and Raynaud's research and, ultimately, finding a cure.

We are committed to investing even more into the most ground breaking and innovative research so that our community can feel the benefit of research sooner. Your donations help us to make this difference and allow us to maintain the crucial investment into research. As part of this commitment, we are very pleased to announce that we have awarded four exciting new grants in June 2018.

As part of this commitment to research, we are very pleased to announce that we have awarded four exciting new grants in June 2018.

Here is an exclusive look at the four grants that we have awarded this year.

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

Dr Angela Tam (Royal Free Hospital/UCL)

Fibrosis (a key feature of scleroderma) is characterised as the thickening of connective tissue, which has very serious complications in systemic scleroderma for large organs such as skin, lungs, heart and the GI system.

This research team will be looking at monocyte cell populations in early scleroderma patients, as well as patients for whom the condition is more established. Monocytes are large white blood cells and comprise part of the immune system response. The research is focused on a particular type of monocyte, which belongs to the non-classical sub population, and has been implicated in fibrosis. Recent research has shown that these particular monocytes are found at higher levels in systemic sclerosis and has a correlation with the level of skin severity.

This work will be able to determine whether these sub populations are also present in patients with early scleroderma, which could lead to the identification of therapeutic targets. The team will be profiling the monocyte sub population, for e.g. determining the cytokine expression profiles, in order to determine the impact of targeting these cells as part of a therapeutic intervention.

“Elicitation of expert prior opinion for a future Bayesian randomised controlled trial for Juvenile Localised Scleroderma (JLS)"

Dr Clare Pain (Alder Hay Children's Hospital)

Although JLS is a rare condition, typically affecting 221 children in the UK, it has very serious implications for the child affected. Methotrexate is typically used in chemotherapy for treatment of cancer, and acts by suppressing the immune system. It is currently the only drug available to treat JLS, however as expected this has toxic side effects that impair quality of life.

Mycophenolate mofetil is a potential alternative treatment that is also used to suppress the immune system and has been typically used in organ transplant procedures. It lowers the immune system just enough to ensure that the host body will not reject the donor organ therefore ensuring the success of the process. 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 cohort numbers. In order to accelerate progress and bring a potentially beneficial treatment to children with JLS sooner, SRUK have funded the setup of a critical expert meeting and panel to design a novel clinical trial that does not rely on large numbers.

In order to carry this trial out, it's crucial that there is consensus amongst clinical experts and leaders in the design of this novel 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.

“Preclinical pathologic signs of SSc in Raynaud's patients at risk of scleroderma"

Dr Francesco del Galdo (University of Leeds) pictured above at SRUK Annual Conference

Raynaud's Phenomenon, in contrast to scleroderma, is fairly common in the UK with up to 10 million diagnosed. Although it is a common condition, a very small sub population of people Raynaud's will exhibit more severe symptoms which could be the precursor to an autoimmune condition such as scleroderma.

While the link between Raynaud's and scleroderma has been known for a number of years, we still don't know why this link exists or what the early signs for progression into scleroderma are.

Dr del Galdo is working with a group of Raynaud's patients who have signs of being at risk for developing scleroderma to determine what factors are at play.

Over 3 years, blood and skin samples will be collected from this group of people at 6-month intervals and analysed to determine the presence of biomarkers (such as antibodies and proteins) associated with scleroderma. While research has taken place into identifying biomarker association with scleroderma, this analysis has only taken place in patients who have been advanced in the progression of their condition. This study takes a novel approach by analysing biomarker association before the onset of scleroderma.

“Using microneedle patches to administer novel anti-fibrotic peptides in order to treat Scleroderma"

Dr Richard Stratton (Royal Free Hospital/UCL)

Skin fibrosis can be a severe and life limiting complication of scleroderma, with an impact on quality of life. It can be progressive and painful leading to permanent ulcers and restriction of movement.

Dr Richard Stratton, based at the Royal Free Hospital in London, will be carrying out a preclinical study investigating the efficacy of a novel treatment for the lesions caused by skin fibrosis.

Working closely with a biotechnology company, Dr Stratton is pioneering the usage of microneedle patches which will deliver a novel therapeutic directly into the skin lesions.

Macrophages, white blood cells that are a part of the immune system, have been implicated in playing a role in the progression of fibrosis through recruitment of other factors into the lesion sites. This may be perpetuating the formation of the lesion and leading to severe presentation. Dr Stratton has determined a peptide that can counteract the effects of macrophages and therefore prevent the progression of the skin lesions.

A significant downside to current available treatment is the toxic side effects that patients often experience. By administering the therapeutics directly to the skin lesions, the toxic side effects can be avoided as the treatment will only affect the lesions and not circulate throughout the body. This treatment has the potential to revolutionise treatment for both localised and systemic scleroderma, and will ultimately result in a significantly better quality of life.

Before this treatment method can progress to a much larger clinical trial, there are key evaluations that need to be carried out. SRUK is supporting Dr Stratton through a grant to evaluate the efficacy of the microneedle patches in 'in vivo' models of skin fibrosis. The adequacy of delivery, local and global effects of the treatment, and toxicity will all be determined in this crucial phase.

If the treatment passes these crucial tests then SRUK will work closely with Dr Stratton to progress the results to clinical trial.

Thank you for reading about the latest research studies we've funded. If you are interested in helping SRUK to fund more work like this, then please visit our donations page here. We rely on the generosity of our community to continue to support groundbreaking research in both scleroderma and Raynaud's.