Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome
Nikita Ikon
Fong-Fu Hsu
Jennifer Shearer
Trudy M.Forte
Robert O.Ryan
摘要：Barth syndrome (BTHS) is a mitochondrial disorder characterized by cardiomyopathy and skeletal muscle weakness.Disease results from mutations in the tafazzin (TAZ) gene,encoding a phospholipid transacylase.Defective tafazzin activity results in an aberrant cardiolipin (CL) profile.The feasibility of restoring the intracellular CL profile was tested by in vivo administration of exogenous CL in nanodisk (ND) delivery particles.Ninety mg/kg CL (as ND)was administered to doxycycline-inducible taz shRNA knockdown (KD) mice once a week.After 10 weeks of CLND treatment,the mice were sacrificed and tissues harvested.Liquid chromatography-mass spectrometry of extracted lipids revealed that CL-ND administration failed to alter the CL profile oftaz KD or WT mice.Thus,although CL-ND were previously shown to be an effective means of delivering CL to cultured cells,this effect does not extend to an in vivo setting.We conclude that CL-ND administration is not a suitable therapy option for BTHS.
机标关键词：
分类号：R963(药理学)
资助基金：grants from the Barth Syndrome Foundation to TF and the National Institutes of Health (R37 HL-64159)
论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：6( 107-112 )
英文信息