DERMATOMICS version 1.0
Research type
Research Study
Full title
DERMATOMICS: Identifying Regulators of Skin Homeostasis
IRAS ID
346054
Contact name
Jake Taylor-King
Contact email
Sponsor organisation
Relation Therapeutics
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Diseases of the skin associated with chronic immune driven conditions, including scleroderma, lupus, dermatomyositis, psoriasis, and atopic dermatitis, significantly impact skin integrity, function, and overall quality of life. These conditions can lead to severe disfigurement, discomfort, and systemic complications, necessitating long-term medical intervention. The prevalence of these skin disorders is rising globally, driven by genetic, environmental, and immunological factors. Unravelling the mechanisms leading to skin manifestations may shed further insights in the overall mechanisms of disease.
We propose a series of linked studies under the DERMATOMICS design to study the aforementioned conditions, starting with this cohort focused on understanding scleroderma/systemic sclerosis (SSc) biology.
Scleroderma or Systemic Sclerosis (SSc) is a highly heterogeneous rare autoimmune fibrotic condition affecting the skin and internal organs. SSc is classified as a Connective Tissue Disease (CTD), a family of conditions including Systemic Lupus Erythematosus, Sjogren Syndrome and Inflammatory Myositis, all characterised by an autoimmune process affecting the connective tissue of most organs, communed by the presence of anti-nuclear antibodies (ANA). In SSc, patients are affected by a combination of tissue and vascular fibrosis, on the background of an often-subtle chronic inflammatory process, leading to the highest per patient morbidity and mortality across CTDs. The main driver of mortality to date is interstitial lung disease (ILD), which is the consequence of the fibrotic involvement of the lungs, leading to a progressive loss of functional lung volumes, and ultimately, derangement of lung circulation, hypoxia, increased risk of hospitalisation for lower respiratory infections and death.
Current treatments for these chronic skin diseases include general immunosuppressive treatments, not necessarily targeted to the specific mechanisms underlying their presentation are primarily symptomatic, focusing on reducing inflammation and managing symptoms rather than addressing the underlying causes. Many of these therapies have limited effectiveness or are burdened with significant side effects. Therefore, there is a critical need to develop a comprehensive understanding of the cellular and molecular mechanisms underlying these skin disorders to identify novel therapeutic targets.
Several factors contribute to the risk and severity of skin diseases, including genetic predisposition, environmental triggers, immune system dysregulation, and lifestyle factors such as diet and smoking. The interactions between these factors are complex and not fully understood. By recruiting patients with scleroderma, we aim to obtain skin punch biopsies for detailed molecular and genetic analysis. To increase the informative value of our study we plan to implement an extreme phenotype approach and include patients with opposite degrees of severity.
Our study aims to elucidate the relationships between the molecular biology of skin cells, skin structure, genetic factors ("DNA"), and environmental influences. The goal is to identify and validate novel therapeutic targets that can lead to more effective and personalised treatment options for chronic skin diseases.
Modern single-cell technologies will be employed to dissect the cellular diversity within the skin. These advanced techniques have revolutionised our understanding of many tissues, but skin tissues remain underexplored, especially in the context of chronic skin diseases. Protocols for skin punch biopsy and single-cell profiling are well-established, allowing us to systematically analyse how genetic variations influence skin structure and function.
REC name
South West - Frenchay Research Ethics Committee
REC reference
24/SW/0104
Date of REC Opinion
18 Sep 2024
REC opinion
Further Information Favourable Opinion