The team at Newcastle University, in collaboration with scientists at Stiefel, a GSK company, have identified how a key skin barrier protein called filaggrin impacts on other proteins and pathways in the skin, which in turn drive the development of eczema.
This has also lead them to identify potential targets for future drug development which could treat the underlying cause rather than treating the symptoms.
Atopic eczema is one of the most common skin conditions in the UK, affecting up to 10% of adults and 20% of children in the UK. It’s more common in children, often developing before their first birthday and often persists into adulthood with severe itching that has profound effects on well-being and may lead to sleep disturbance.
The research builds on the important discovery by scientists in Dundee which showed that lack of the protein filaggrin in the skin caused an inherited dry skin condition known as ichthyosis vulgaris that is strongly linked to the development of atopic eczema, as well as other allergic diseases such as hay fever and asthma.
Lead for this study, Nick Reynolds is Professor of Dermatology at Newcastle University, and Deputy Lead for the Skin & Oral Disease theme with the NIHR Newcastle Biomedical Research Centre. As a Consultant Dermatologist, he also sees patients with skin conditions including eczema at Newcastle’s Royal Victoria Infirmary. He said: “We have shown for the first time that loss of the filaggrin protein alone is sufficient to alter key proteins and pathways involved in triggering eczema. This research reinforces the importance of filaggrin deficiency leading to problems with the barrier function in the skin and predisposing someone to eczema.”
Publishing in the Journal of Allergy and Clinical Immunology (JACI), researchers at Newcastle University, in collaboration with scientists at Stiefel GSK, report on their development of a human model system. In this, the upper layer of skin (epidermis) was modified, using molecular techniques, to become filaggrin-deficient, directly mimicking the situation observed in the skin of patients with atopic eczema.
This model enabled the team to discover proteins and signalling pathways directly down-stream of filaggrin, and most importantly, identified a number of key regulatory mechanisms. These included regulators of inflammatory signalling, cell structure, barrier function and stress response. These pathways were found to map to those networks observed in the skin of people with active eczema.
This mapping provides researchers with new understanding of the mechanisms involved and suggests targets for future drug development.
Nina Goad of the British Association of Dermatologists said: “This latest research from Newcastle is crucial as it expands on our knowledge of how filaggrin impacts on other proteins and pathways in the skin, which in turn trigger the disease. This type of research allows scientists to develop treatments that target the actual root cause of the disease, rather than just managing its symptoms. Given the level of suffering eczema causes, this is a pivotal piece of research.”
This research was supported by Knowledge Transfer Partnership, the BBSR, and was carried out in facilities supported by the NIHR Newcastle Biomedical Research Centre. Collaborative research of this kind underscores the benefit of research programmes that support academic pharma partnerships, and highlights the value of clinical research which is supported through the NIHR Newcastle BRC.
The NIHR Newcastle Biomedical Research Centre is a partnership between Newcastle Upon Tyne Hospitals NHS Foundation Trust (which includes the Royal Victoria Infirmary) and Newcastle University. This partnership harnesses world-class expertise to ensure patients benefit sooner from new treatments, diagnostics and prevention strategies in long-term diseases affecting the older person.