Ikon Nikita, Hsu Fong-Fu, Shearer Jennifer, Forte Trudy M, Ryan Robert O
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
Department of Medicine, School of Medicine, Washington University, St. Louis, MO 63110, USA.
J Biomed Res. 2018 Mar 26;32(2):107-112. doi: 10.7555/JBR.32.20170094.
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 CL-ND 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 of taz 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.
巴斯综合征（BTHS）是一种线粒体疾病，其特征为心肌病和骨骼肌无力。该疾病由tafazzin（TAZ）基因突变引起，TAZ基因编码一种磷脂转酰基酶。tafazzin活性缺陷导致心磷脂（CL）谱异常。通过在体内给予纳米盘（ND）递送颗粒中的外源性CL，测试了恢复细胞内CL谱的可行性。每周一次给强力霉素诱导的taz短发夹RNA敲低（KD）小鼠施用90mg/kg CL（作为ND）。CL-ND治疗10周后，处死小鼠并采集组织。提取脂质的液相色谱-质谱分析显示，施用CL-ND未能改变taz KD或野生型（WT）小鼠的CL谱。因此，尽管CL-ND先前被证明是将CL递送至培养细胞的有效手段，但这种效果在体内环境中并不适用。我们得出结论，施用CL-ND不是BTHS的合适治疗选择。
