Our Community Blog A British Skin Foundation funded project into atopic eczema March 2019 Human beta-defensin in Atopic Dermatitis: dissecting the mechanism of a novel, targetable, protection against skin barrier damage. Professor Donald J. Davidson is an Inflammation Biologist and Senior Researcher at the University of Edinburgh Centre for Inflammation Research. Professor Davidson was awarded a British Skin Foundation Large Grant, entitled ‘Human beta-defensin in Atopic Dermatitis: dissecting the mechanism of a novel, targetable, protection against skin barrier damage’, supporting a PhD student, Jennifer Shelley, to conduct research into this topic, starting in the autumn of 2018. Here Donald and Jennifer explain the research in more detail and what they hope they can achieve. What is the problem? Atopic Dermatitis (AD), commonly known as atopic eczema, is a common, distressing skin disease. We all know somebody affected by it or have experienced it ourselves. It results in areas of itchy, red, broken skin, typically on the face, scalp and limbs, where the skin is inflamed. In the UK, as many as 20% of children, and up to 10% of adults, have AD. AD is a chronic condition, so it flares up repeatedly and can affect people for their whole lives. As a result, treatments need to be used long-term from an early age. Therefore, it is really important that these treatments are safe and well tolerated. AD costs the NHS over £47 million/year, with use of corticosteroids on the skin being the current main form of treatment. These can work well for a lot of people, but they can have damaging side effects over long term use, including interfering with the body’s natural responses to skin infection. In addition, in some people, these corticosteroids do not work well or they stop being effective. There are not many other good treatment options for these people and those that are available can have more harmful side effects. For most of the people you know that have eczema, the condition may seem like a relatively minor problem. But, for a significant proportion, the disease can be very extensive, painful, hard to treat and have a genuinely disabling impact on their lives. It is therefore clear that medical researchers and clinicians need to development new therapies for AD. This will be done most effectively if we have a stronger understanding of how the disease develops and progresses, and what prevents it from occurring in people who are not affected. We can then target new treatments based on that knowledge. Funding for research in this area, such as grants from the British Skin Foundation (BSF), enables laboratories like ours to try to start to tackle this problem. In this manner, the BSF can translate donations and the fund-raising work of their supporters into efforts to improve the lives of individuals with AD in the future. Research can be a long hard process, but it offers a light at the end of the tunnel. How can we try to tackle the problem? One important feature of AD is disruption to the barrier function of the skin. Recent clinical studies suggest that restoring and/or maintaining effective skin barrier function is a promising strategy to explore. Skin barrier disruption in AD has been linked to a wide range of factors, including environmental irritants, and an individual’s genetics. It can also be affected by skin infections and by the types of bacteria an individual has living on their skin; some of which seem to be more protective, while others may be more harmful. For example, the bacteria Staphylococcus aureus, more commonly found on the skin of people with AD than those without AD, can produce barrier-damaging substances called proteases that may contribute to the disease process. If we can find ways to block the barrier damage caused by these proteases, and to tip the balance towards more protective bacteria on the skin, perhaps we can move towards new treatments for AD. But what kind of substances could have those properties? Donald, and the researchers he works with, study substances called Antimicrobial Host Defence Peptides (HDP). These are naturally produced by all animals, and even by plants. HDP can kill harmful bacteria, viruses and fungi, can alter the balance of the types of bacteria living on our bodies, and can direct and adapt the approaches our bodies choose to use to fight infections. The team discovered that one HDP, called human beta-defensin (hBD)2, can also protect the skin barrier from damage caused by proteases in a laboratory setting. Intriguingly, this hBD2 is produced naturally by the skin, and, whereas healthy skin makes more of it when faced with inflammation, damage or infection, AD skin is less effective at responding in this way and launching a protective hBD2 response. So, can studying hBD2 help us develop a new treatment for AD, based on a naturally occurring skin HDP? Might it help kill harmful bacteria, select for more protective bacteria, and block the damaging effects of bacterial proteases to protect the skin’s barrier function? That’s what our team are hoping! Jennifer started her PhD in the autumn of 2018. With supervision from Donald and other members of the group, she is now getting to grips with the varied laboratory techniques required to start to develop this research proposal. It is early days. But, as she learns these skills and a working knowledge of the research topic, she has the type of exciting future prospects that sustains a medical researcher through the days when experiments are not working; namely that, thanks to BSF funding, she just might make the kind of breakthrough that ultimately leads to the development of a new, safe, long-term treatment approach for AD. For more information see Donald’s websites at: www.djdavidsonlab.net www.ed.ac.uk/inflammation-research/people/principal-investigators/dr-donald-j-davidson or follow Donald and Jennifer on twitter. Professor Donald J. Davidson and Jennifer Shelley Donate to research Rebecca's story Find out more about eczema By donating to skin disease research you are helping us to find treatments and cures for common conditions like eczema, acne and psoriasis through to potential killers like melanoma skin cancer. Thank you.