Targeting NTRK1 for Treatment of Allergic Inflammatory Conditions
Summary
Pharmacological targeting of NTRK1 using small molecule inhibitors may reduce allergic inflammation.
Overview
IL-13 and neutrophins are functionally important to the pathogenesis of allergic disease. Drs. Rothenberg and Rochman have discovered that in epithelial cells, NTRK1 (a high-affinity receptor for nerve growth factor, NGF) is an early transcriptional target of IL-13. Furthermore, in epithelial cells, IL-13 and NGF synergistically express genes important to allergic disease, including eotaxin-3 (CCL26). In a model of eosinophilic esophagitis (EoE), NTRK1 was increased and dynamically expressed as a function of disease activity, while its ligand NGF was constitutively expressed in control and disease states. This suggests that IL-13 stimulated NTRK1 induction is a limiting factor in pathway activation. Pharmacological inhibition of NTRK1 may be a novel and important mechanism for limiting allergic disease pathogenesis.
Applications
Therapeutic treatment of allergic inflammatory conditions
Value Proposition
- Commercially available, highly specific NTRK1 inhibitors are available for use
- Targets a wide range of eosinophilic disorders
- Reapplication of lestaurtinib (CEP-701), and crizotinib
Market Overview
Eosinophilic disorders range from the very common, such as asthma and atopic dermatitis, which affect nearly 8% and 9-30% of the US population respectively, to rare diseases such as eosinophilic gastroenteritis (10/100,000) and hypereosinophilic syndrome.
Investigator
Marc E. Rothenberg, MD, PhD & Marc Rochman, PhD, Division of Allergy and Immunology
