Translational impact of omics studies in alopecia areata: recent advances and future perspectives

ABSTRACT

Introduction

Alopecia areata (AA) is a non-scarring, hair loss disorder and a common autoimmune-mediated disease with an estimated lifetime risk of about 2%. To date, the treatment of AA is mainly based on suppression or stimulation of the immune response. Genomics and transcriptomics studies generated important insights into the underlying pathophysiology, enabled discovery of molecular disease signatures, which were used in some of the recent clinical trials to monitor drug response and substantiated the consideration of new therapeutic modalities for the treatment of AA such as abatacept, dupilumab, ustekinumab, and Janus Kinase (JAK) inhibitors.

Areas covered

In this review, genomics and transcriptomics studies in AA are discussed in detail with particular emphasis on their past and prospective translational impacts. Microbiome studies are also briefly introduced.

Expert opinion

The generation of large datasets using the new high-throughput technologies has revolutionized medical research and AA has also benefited from the wave of omics studies. However, the limitations associated with JAK inhibitors and clinical heterogeneity in AA patients underscore the necessity for continuing omics research in AA for discovery of novel therapeutic modalities and development of clinical tools for precision medicine.

KEYWORDS:

• alopecia areata
• biomarkers
• genomics
• GWAS
• JAK/STAT pathway
• JAK inhibitors
• personalized medicine
• precision medicine
• transcriptomics
• translational research

Article highlights

• Two genome-wide association studies (GWAS) of AA implicated common genetic variants at 14 individual loci to be associated with disease risk.

• The mechanistic follow-up of a GWAS locus in mice and human using transcriptome profiling provided novel insights into the pathobiology of AA, which contributed together with clinical case reports to the initiation of clinical trials of JAK inhibition in AA.

• Clinical studies revealed that more than 60% of AA patients respond to small molecule JAK inhibitors approved by FDA for treatment of other conditions. Phase 2 and 3 clinical trials are going. However, a high demand persists for the discovery of other therapeutic modalities due to the 30% of AA patients not responding to JAK inhibition and other limitations concerning cost-affordability, adverse effects and high rates of relapse after cessation of JAK inhibition therapy.

• Transcriptome profiling studies in AA identified consistent molecular signatures of disease that can be used to evaluate disease status and were used to monitor drug response on a molecular level in several clinical trials.

• Several studies have shown that application of computational biology tools on transcriptome data from scalp skin may hold important potential for the development of clinical tools for prediction of prognostic factors or drug response in AA.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer has acted as a consultant for Pfizer, site PI for Pfizer clinical trials on JAK inhibitors, and declare that their institution has received research funding. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), under the auspices of the Germany Excellence Strategy - EXC2151-390873048 (to R Betz).