Biotherapeutic Approaches in Atopic Dermatitis

Abstract

The skin microbiome plays a central role in inflammatory skin disorders such as atopic dermatitis (AD). In AD patients, an imbalance between pathogenic Staphylococcus aureus (S. aureus) and resident skin symbionts creates a state of dysbiosis which induces immune dysregulation and impairs skin barrier function. There are now exciting new prospects for microbiome-based interventions for AD prevention. In the hopes of achieving sustained control and management of disease in AD patients, current emerging biotherapeutic strategies aim to harness the skin microbiome associated with health by restoring a more diverse symbiotic skin microbiome, while selectively removing pathogenic S. aureus. Examples of such strategies are demonstrated in skin microbiome transplants, phage-derived anti-S. aureus endolysins, monoclonal antibodies, and quorum sensing (QS) inhibitors. However, further understanding of the skin microbiome and its role in AD pathogenesis is still needed to understand how these biotherapeutics alter the dynamics of the microbiome community; to optimize patient selection, drug delivery, and treatment duration; overcome rapid recolonization upon treatment cessation; and improve efficacy to allow these therapeutic options to eventually reach routine clinical practice.

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

“…Several distinct strategies to restore or modulate the composition of the skin microbiome have been proposed [38][39][40] . Microbiome transplantation and bacterial replacement Fig.…”

Skin dysbiosis in the microbiome in atopic dermatitis is site-specific and involves bacteria, fungus and virus

“…Using phages for targeting microbial dysbiosis in AD yields potential, which is supported by the specificity of phages [ 45 ]. Phage-derived endolysins have been used to target S. aureus specifically, however not in AD patients [ 46 ].…”

Future trends in synthetic biology in Asia

“…118 The repertoire of engineered immune cells is also being expanded beyond T-cells to include NK cells 119 and macrophages. 120 In addition to immune cells, engineered bacteria, single species or multi-species consortia, are also being developed for skin, gastrointestinal, and other microbiome-associated diseases, [121][122][123][124] and notably for systemic metabolic diseases, where the most advanced developments are already in human clinical trials for phenylketonuria. 125,126 Closely related are bacteriophages as highly potent and specific antimicrobials 127 ; engineered phages were also developed as modulating agents to enhance the effect of chemotherapy in cancer treatment.…”