Ufuk Mert1,2, Can Müftüoğlu1, Sevgi Erdem1, Aygül Sadıqova3, Seray Toz4, Yusuf Ozbel4, Ayse Caner5,6,7. 1. Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey. 2. Atatürk Health Care Vocational School, Ege University, Izmir, Turkey. 3. Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. 4. Department of Parasitology, Faculty of Medicine, Ege University, Izmir, Turkey. 5. Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey. ayse.caner@ege.edu.tr. 6. Department of Parasitology, Faculty of Medicine, Ege University, Izmir, Turkey. ayse.caner@ege.edu.tr. 7. Cancer Research Center, Ege University, Izmir, Turkey. ayse.caner@ege.edu.tr.
Abstract
PURPOSE: Leishmaniasis is a neglected infectious disease affecting millions of people worldwide. Visceral leishmaniasis (VL), caused by Leishmania infantum and Leishmania donovani, is one of the main clinical forms of the disease and fatal if not treated promptly and properly. Despite being available for the last 70 years, current drugs used in the treatment of leishmaniasis have serious problems as they have high toxicity, require long-term administration and cause serious side-effects, leading to the emergence of resistant and relapse cases. Therefore, there is an urgent need for the discovery of novel antileishmanial molecules and the development of new treatment regimens. The drug used for chemotherapy of B-cell malignancies, Ibrutinib, an inhibitor of Bruton's Tyrosine Kinase (BTK), can offer a new therapeutic perspective due to the functions of BTK on intracellular signaling mechanism of macrophages, which are the primary resident cell for Leishmania. Hence, the study aimed to evaluate ibrutinib as a potential anti-Leishmanial drug. METHOD: In this study, we evaluated the antileishmanial effect of Ibrutinib by in vitro L. infantum infection model using macrophages, with cell viability assay, parasite rescue assay, real-time qPCR. RESULTS: We showed that Ibrutinib was significantly more effective than the Glucantime against L. infantum. In addition, our data revealed that Ibrutinib inhibited parasite growth and load without impairing macrophage viability. CONCLUSIONS: Consequently, due to its efficacy and safety, Ibrutinib may be a promising candidate for the treatment of VL caused by L. infantum as a host-targeted drug.
PURPOSE: Leishmaniasis is a neglected infectious disease affecting millions of people worldwide. Visceral leishmaniasis (VL), caused by Leishmania infantum and Leishmania donovani, is one of the main clinical forms of the disease and fatal if not treated promptly and properly. Despite being available for the last 70 years, current drugs used in the treatment of leishmaniasis have serious problems as they have high toxicity, require long-term administration and cause serious side-effects, leading to the emergence of resistant and relapse cases. Therefore, there is an urgent need for the discovery of novel antileishmanial molecules and the development of new treatment regimens. The drug used for chemotherapy of B-cell malignancies, Ibrutinib, an inhibitor of Bruton's Tyrosine Kinase (BTK), can offer a new therapeutic perspective due to the functions of BTK on intracellular signaling mechanism of macrophages, which are the primary resident cell for Leishmania. Hence, the study aimed to evaluate ibrutinib as a potential anti-Leishmanial drug. METHOD: In this study, we evaluated the antileishmanial effect of Ibrutinib by in vitro L. infantum infection model using macrophages, with cell viability assay, parasite rescue assay, real-time qPCR. RESULTS: We showed that Ibrutinib was significantly more effective than the Glucantime against L. infantum. In addition, our data revealed that Ibrutinib inhibited parasite growth and load without impairing macrophage viability. CONCLUSIONS: Consequently, due to its efficacy and safety, Ibrutinib may be a promising candidate for the treatment of VL caused by L. infantum as a host-targeted drug.
Authors: S Sundar; D K More; M K Singh; V P Singh; S Sharma; A Makharia; P C Kumar; H W Murray Journal: Clin Infect Dis Date: 2000-10 Impact factor: 9.079
Authors: Lee A Honigberg; Ashley M Smith; Mint Sirisawad; Erik Verner; David Loury; Betty Chang; Shyr Li; Zhengying Pan; Douglas H Thamm; Richard A Miller; Joseph J Buggy Journal: Proc Natl Acad Sci U S A Date: 2010-07-06 Impact factor: 11.205
Authors: Julius Lukes; Isabel L Mauricio; Gabriele Schönian; Jean-Claude Dujardin; Ketty Soteriadou; Jean-Pierre Dedet; Katrin Kuhls; K Wilber Quispe Tintaya; Milan Jirků; Eva Chocholová; Christos Haralambous; Francine Pratlong; Miroslav Oborník; Ales Horák; Francisco J Ayala; Michael A Miles Journal: Proc Natl Acad Sci U S A Date: 2007-05-21 Impact factor: 11.205