biostudies-literatureMantuano PPRIN – MIUR1742https://www.ebi.ac.uk/biostudies/studies/S-EPMC8615430biostudies-literatureUnknown11(11)ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mdx mice, a 4-week subcutaneous treatment with dasatinib (DAS), a pan-Src-TKs inhibitor approved as anti-leukemic agent, increased muscle β-DG, with minimal amelioration of morphofunctional indices. To address possible dose/pharmacokinetic (PK) issues, a new oral DAS/hydroxypropyl(HP)-β-cyclodextrin(CD) complex was developed and chronically administered to mdx mice. The aim was to better assess the role of β-DG in pathology progression, meanwhile confirming DAS mechanism of action over the long-term, along with its effBiomoleculesβ-Dystroglycan Restoration and Pathology Progression in the Dystrophic mdx Mouse: Outcome and Implication of a Clinically Oriented Study with a Novel Oral Dasatinib Formulation.PMC8615430DPP NL 2015 Grant entitled “Preclinical studies to validate cSrc tyrosine kinase as therapeutic target in Duchenne muscular dystrophy”projects n. D908ACB4 (S.C.) and 50646C43 (E.C.)project n. AIM1801289-2 (P.M.)Prot. 2017FJSM9S_005Boccanegra BDe Bellis MCutrignelli ASanarica FArduino ICappellari ODenora NMele AConte ECirmi SLopedota AADe Luca AMantuano Pfalseβ-Dystroglycan Restoration and Pathology Progression in the Dystrophic mdx Mouse: Outcome and Implication of a Clinically Oriented Study with a Novel Oral Dasatinib Formulation.ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mdx mice, a 4-week subcutaneous treatment with dasatinib (DAS), a pan-Src-TKs inhibitor approved as anti-leukemic agent, increased muscle β-DG, with minimal amelioration of morphofunctional indices. To address possible dose/pharmacokinetic (PK) issues, a new oral DAS/hydroxypropyl(HP)-β-cyclodextrin(CD) complex was developed and chronically administered to mdx mice. The aim was to better assess the role of β-DG in pathology progression, meanwhile confirming DAS mechanism of action over the long-term, along with its eff2021-01-01T00:00:00Z2021 Nov2025-05-29T22:27:37.794Z2022-02-11T13:15:06.74ZS-EPMC86154303482774010.3390/biom11111742