Treating Fibrosis in Scleroderma: SRUK-funded study lays groundwork for potential new treatment for scleroderma-related skin fibrosis

SRUK has recently supported a new study that aims to help enable effective and painless treatment for fibrosis in people living with scleroderma.

Fibrosis, which leads to excessive thickening or scarring of the body’s tissues, is a characteristic symptom of systemic sclerosis which can affect multiple organs in the body including the skin, lungs, gastrointestinal tract, heart, blood vessels, and kidneys. This can lead to an array of debilitating complications and potentially a high level of physical disability, which together can have a considerable impact on everyday life.

Findings from an exciting and recently-completed research project, led by Dr Richard Stratton and funded by SRUK in 2018, may open a new therapeutic avenue for the treatment of skin fibrosis.

About fibrosis

We are all familiar with what happens to our skin following an injury, like a cut or a graze. As part of the wound healing process, a scar is formed over the damaged area. The scar is formed as the result of specialised cells called fibroblasts depositing collagen over the damaged area. This usually allows the correct amount of scar tissue to form: enough to patch over the wound but not so much to over-stiffen the tissue. However, in scleroderma these processes do not function as normal, with excessive fibroblast activity leading to the overproduction of collagen and the stiffening of the tissues which make up the skin and internal organs.  

The reason why fibroblasts are active in people with scleroderma when there is an absence of actual ‘damage’ to the skin is still not fully understood. However, evidence suggests that the immune system is the culprit - with one type of cell, the macrophage (the ‘pac-man’ of the immune system responsible for gobbling up debris such as dying cells and bacteria), being implicated as a driver of the excessive fibrotic response.

What did the team do?

The current project, led by Dr Stratton’s team, set out to investigate whether a small and relatively simple protein molecule known as a ‘peptide’, which was developed by a US based biotechnology company called Riptide Bioscience, has potential as a therapeutic in treating fibrosis. Dr Stratton’s team has collaborated with Riptide before, and this current project builds upon the findings of previous research also supported by SRUK which studied these peptides. Previous work by the team showed that some peptides could block fibrosis by preventing pro-fibrotic macrophages from communicating with fibroblasts. Furthermore, these peptides can also prevent the growth and development of new pro-fibrotic macrophages.

Before these peptides can be tested in humans they must first be tested for toxicity and efficacy in pre-clinical models of scleroderma. The team set about initiating testing in mouse and human tissue models of scleroderma. They were particularly interested in preventing the progressive and disabling effects on the skin that the condition causes. They decided to test whether the peptide could be targeted locally to the skin (as opposed to being taken as a tablet or an infusion into a vein), using a new method of drug delivery to the skin known as microneedles, to directly deliver the peptide to the skin of mice. A more targeted approach to drug delivery could reduce any potential side effects and the use of microneedles which are applied via skin patches like in modern blood glucose measuring devices could facilitate easy treatment at home.  

Conclusions

Dr Stratton’s team found that the peptide, administered via microneedles, may effectively inhibit scleroderma-like fibrosis in human-tissue models, and in mice. This offers up new hope of a potential therapeutic avenue and an effective and pain-free way of delivering this to people living with scleroderma.  

Of course, more research is required if this therapeutic is to enter the clinic. More extensive pre-clinical work such as further toxicity testing will be required, along with the need to secure funding to support clinical trials in a small number of targeted patients. The microneedle patches used are already FDA-approved and CE marked for use in humans, which means that if the therapy is found to be safe and effective in humans by any eventual clinical trial then it’s delivery via microneedles could become a reality. 

SRUK hopes that this research will lead to an effective, pain-free therapy with lower side effects for those with scleroderma, helping to combat the debilitating effects of widespread skin fibrosis.