Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines.

ABSTRACT:

Purpose

Noonan syndrome with multiple lentigines (NSML) is an autosomal dominant disorder presenting with hypertrophic cardiomyopathy (HCM). Up to 85% of NSML cases are caused by mutations in the PTPN11 gene that encodes for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2). We previously showed that low-dose dasatinib protects from the development of cardiac fibrosis in a mouse model of NSML harboring a Ptpn11^Y279C mutation. This study is performed to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties of a low-dose of dasatinib in NSML mice and to determine its effectiveness in ameliorating the development of HCM.

Methods

Dasatinib was administered intraperitoneally into NSML mice with doses ranging from 0.05 to

SUBMITTER: Yi JS 

PROVIDER: S-EPMC9270274 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature