ECZOMICS version 1.0
Research type
Research Study
Full title
ECZOMICS: Understanding the Cellular and Genetic Basis of Atopic Dermatitis Response and Resistance
IRAS ID
359622
Contact name
David Roblin
Contact email
Sponsor organisation
Relation Therapeutics
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
6 years, 0 months, 0 days
Research summary
Atopic Dermatitis (AD) is a highly heterogeneous, chronic inflammatory skin disorder that significantly impacts skin function, appearance, and overall quality of life. Characterised by intense pruritus, recurring eczematous lesions, and a relapsing disease course, AD affects individuals of all ages and can lead to substantial physical discomfort, psychological distress, and social stigma. The disease burden is compounded by the chronicity of symptoms and the need for long-term management, often involving multiple therapeutic modalities. The global prevalence of AD is increasing, influenced by environmental changes, immune dysregulation, and complex gene-environment interactions.
Modern therapeutic advances, particularly biologics targeting the Th2 immune axis (e.g., Dupilumab), have transformed care for some patients. However, clinical experience and emerging molecular evidence suggest that AD cannot be fully explained by Th2-dominant immunopathology alone. A significant proportion of patients exhibit suboptimal response or non-response to current therapies, highlighting the involvement of additional immune pathways, notably those driven by Th1, Th17, and Th22 T-cell subsets.
Despite evidence implicating Th22 biology in a subset of patients - with some promising results from agents like fezakinumab and temtokibart—there is limited efficacy from targeting Th1 and Th17 pathways directly. This complexity underscores the need to move beyond broad immunosuppression or single-pathway inhibition, toward a more granular, cell-type-specific understanding of disease heterogeneity and treatment response.
Current treatments for AD, though often effective in symptom control, are not universally beneficial and may not address the root molecular causes in all patients. To provide a reference baseline for disease-specific molecular patterns, a cohort of healthy volunteers without AD will also be enrolled. Broad immunosuppressants such as JAK inhibitors or PDE4 inhibitors provide systemic benefit but raise safety concerns with chronic use. As such, there remains a critical unmet need to uncover the mechanistic diversity underpinning AD to inform new therapeutic targets that are more precise and personalised.To address this, the ECZOMICS study will employ high-resolution genomic and cellular technologies to investigate the skin microenvironment in AD. We aim to explore how inherited genetic variation manifests at the level of gene expression and immune cell behaviour, both in treatment-naïve states and following systemic intervention. Our hypothesis is that transcriptional profiling at single-cell resolution, combined with whole genome sequencing and proteomic analysis, will enable us to map immune dysfunction in a patient-specific and pathway-resolved manner. We will collect lesional and non-lesional skin punch biopsies from moderate to severe AD patients, including both biologic-naive and systemic treatment failure cohorts, as well as healthy controls, prior to and after treatment initiation. By stratifying patients into systemic treatment responders and non-responder groups (e.g. based on EASI improvement at 12 weeks), we aim to capture mechanistic differences that determine therapeutic outcomes. This approach will allow us to test the hypothesis that distinct cellular ecosystems and regulatory networks underlie treatment resistance and disease severity.
The integration of single-cell transcriptomics, whole genome sequencing, and blood-based proteomics using the Rosalind platform (Relation Therapeutics) will provide a systems-level view of AD biology. This strategy will enable the identification of novel cell-type-specific drivers of disease and candidate targets for next-generation therapeutic development.
In doing so, ECZOMICS aims not only to improve our understanding of AD pathophysiology but also to build a translational bridge between clinical presentation, underlying molecular mechanisms, and future personalised therapies.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
25/LO/0830
Date of REC Opinion
9 Jan 2026
REC opinion
Further Information Favourable Opinion