Targeting the JAK-STAT pathway in the treatment of ‘Th2-high’ severe asthma

Abstract

Severe asthma is a heterogeneous disease characterized by reversible airway obstruction, chronic inflammation and airway remodeling. Phenotyping and/or endotyping can lead to a more personalized treatment strategy, improving the efficacy of novel drugs. Atopic asthma is associated with high levels of Th2 cells, implicated in a number of inflammatory responses. Differentiation of these cells from naive T cells occurs primarily via the JAK-STAT signaling pathway. Targeting this pathway through inhibition of activating cytokines (IL-4 and IL-13) and their receptors, the JAKs or the STATs, has been shown to have a therapeutic effect on asthma pathology. There are a number of novel drugs currently in development, which target various pathway components; these include both biologics and small molecules at various stages of development.