Targeting Molecular Pathways for Atopic Dermatitis Therapy: An Overview

This study provides a review of Molecular Pathways and the Future Therapeutic Implications for Atopic Dermatitis. No available treatments can provide long-term remission for patients with moderate to severe Atopic Dermatitis (AD) creating a large unmet need for effective systemic treatment. Together with asthma and allergic rhinitis, it constitutes the “Atopic Triad”. The important factors and related mechanisms for AD are the following: (a) Genetic, (b) Neurohumoral, (c) Skin barrier dysfunction, and (d) Immunological mechanisms. Much progress has been made in the understanding of its genetic background and pathophysiology through studies in genetics, epidemiology, and immunology. The cellular interactions, molecular events, and pathways for the pathogenesis of AD were integrated into a hypothesis and reported recently. As the new insights into the immune and molecular pathways of AD increase, a variety of experimental agents, particularly biological agents that target pathogenic molecules bring promise of safe and effective therapeutics. Some of the most promising biological therapies that are in development or in clinical trials are based on principles as the following: Barrier repair, Allergen-specific immunotherapy, Targeted Immunomodulating Therapies (TIT) (Anti-IgE therapy, Anti-CD20, Inhibition of T-cell responses, Th2-cell inhibition strategies/ Anti IL-4 therapies, Anti IL-5 strategies, Anti IL-31), Targeting Th22, Targeting Th17/IL-12/IL-23 pathway, Recombinant IFN-y, Anti IL-6R, Anti TNF agents, Phosphodiesterase inhibitors, PPAR-gamma agonists.

All these biological therapies are at different phases of clinical trials. There has been a growing trend toward the use of targeted therapies in treating AD in recent years. These biological agents would potentially hold great promise for the treatment of AD if they can offer advantages, i.e. low toxicity, good efficacy, improved patient compliance via weekly/biweekly/and even monthly administration, reduction of disease activity, relapse prevention, etc. In Summary, the recent advances in understanding the immunopathogenic mechanisms provide an opportunity for the development of biological therapies directed at pathways driving AD. This is possibly the beginning of an exciting era in AD therapeutics with the impending availability of drugs having low toxicity and increased patient compliance. These expected drugs will not only treat this disease but also prevent the development and relapse of new skin lesions. In this article, attempts have been made to provide an updated account of these new possibilities. The recent advances in our understanding of the immunopathogenic mechanisms implicated in AD provide an opportunity for the development of biological therapies directed at pathways driving AD.