Imatinib ameliorates bronchiolitis obliterans via inhibition of fibrocyte migration and differentiation

Abstract

Background: Imatinib, a tyrosine kinase inhibitor, has been proposed as a potential antifibrotic agent

Loading Imatinib inside targeted nanoparticles to prevent Bronchiolitis Obliterans Syndrome

“…The choice to use Imatinib as a drug to be encapsulated into GNPs was based on different reasons. (a) It has been proven that Imatinib is a potent anti-fibrotic drug through the inhibition of cAbl leading to a reduction of cell proliferation, anti-apoptotic signaling and migration 7 , 8 , 10 , 14 . (b) Imatinib antifibrotic effect has already been demonstrated on the HTT model administered daily by intraperitoneal route 8 .…”

“…Moreover, ILD and BOS have in common the limited knowledge about the exact molecular mechanisms underlying the origin of LFs and the absence of an effective therapy. Thus, we decided to study the toxic efficacy of delivering Imatinib (GNP-HCIm), a tyrosine kinase inhibitor with known antifibrotic properties 7 , 8 , through tracheal instillation in a mouse model of bleomycin-induced pulmonary fibrosis, demonstrating a significant reduction of the fibrotic lesions and macrophages activity modulation 5 . Given these encouraging results, here, we wanted to assess the efficacy of delivering locally Imatinib by GNP-HC in a mouse model of BOS, since the use of a nanovehicle could increase lung deposition of drug limiting extrapulmonary side effects.…”

Prevention of bronchiolitis obliterans—the realization of a hope?

“…1 Bronchiolitis obliterans is a frequent and disabling complication after lung transplantation, occurring in >50% of lung transplant recipients within 5 years of the transplant. 2 Current treatments are only partially effective and include increasing immunosuppression and administering low-dose macrolide antibiotics, leukotriene-receptor antagonists and combinations of inhaled bronchodilators and glucocorticoids. 1 Because of the multiplicity of mechanisms causing the initial lesion to the epithelial surfaces of the bronchi, involving both innate and adaptive immunity responding either to allo-antigens or infectious/toxic insults, 1 prevention of the initial lesions may not be possible or feasible in time to prevent the fibrotic response.…”

“…In this issue, Watanabe et al 2 report that imatinib, a specific tyrosine kinase inhibitor, prevents obstruction of the airways in the heterotopic tracheal transplantation animal model of bronchiolitis obliterans. The anti-fibrotic properties of imatinib, were first described by Daniels et al 3 and Aono et al 4 more than 10 years ago.…”

“…With their report in this issue of JHLT , 2 the authors begin to address how imatinib may prevent fibrosis in the context of transplantation. They show how imatinib prevents fibrosis by 2 mechanisms.…”