Drug-induced mast cell eradication: A novel approach to treat mast cell activation disorders?

Abstract

Mast cell (MC) activation is a key event in allergic reactions, other inflammatory states, and MC activation syndromes. MC-stabilizing agents, mediator-targeting drugs, and drugs interfering with mediator effects are often prescribed for these patients. However, the clinical efficacy of these drugs varies depending on the numbers of involved MCs and the underlying pathology. One straightforward approach would be to eradicate the primary target cell. To date however, no MC-eradicating treatment approach has been developed for patients with MC activation disorders. Nevertheless, recent data suggest that long-term treatment with agents effectively inhibiting KIT function results in the virtual eradication of tissue MCs and a sustained decrease in serum tryptase levels. In many of these patients, MC depletion is associated with a substantial improvement in mediator-induced symptoms. In patients with an underlying KIT D816V-positive mastocytosis, such MC eradication requires an effective inhibitor of KIT D816V, such as avapritinib. However, the use of KIT inhibitors must be balanced against their potential side effects. Here we discuss MC-eradicating strategies in various disease models, the feasibility of this approach, available clinical data, and future prospects for the use of KIT-targeting drugs in MC activation disorders.

• Authors: Peter Valent, Cem Akin, Karin Hartmann, Andreas Reiter, Jason Gotlib, Karl Sotlar, Wolfgang R Sperr, Lina Degenfeld-Schonburg, Dubravka Smiljkovic, Massimo Triggiani, Hans-Peter Horny, Michel Arock, Stephen J Galli, Dean D Metcalfe
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 149 Issue 6 Pg. 1866-1874 (06 2022) ISSN: 1097-6825 [Electronic] United States
• PMID: 35421448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Proto-Oncogene Proteins c-kit
• Staurosporine

Topics

• Humans
• Mast Cell Activation Disorders
• Mast Cells (pathology)
• Mastocytosis (drug therapy, pathology)
• Mastocytosis, Systemic (drug therapy)
• Proto-Oncogene Proteins c-kit (genetics)
• Staurosporine (therapeutic use)