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Nikita Ikon,Fong-Fu Hsu,Jennifer Shearer,Trudy M. Forte,Robert O. Ryan.Journal of Biomedical Research,2018,32(2):107-112
Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome
Received:August 19, 2017  Revised:September 16, 2017
DOI10.7555/JBR.32.20170094
Keywordsmitochondria, cardiomyopathy, nanoparticles, drug delivery
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AuthorInstitution
Nikita Ikon Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
Fong-Fu Hsu Department of Medicine, School of Medicine, Washington University, St. Louis, MO 63110, USA
Jennifer Shearer Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
Trudy M. Forte Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
Robert O. Ryan Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA;Department of Biochemistry, University of Nevada, Reno, NV 89557, USA
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Abstract
      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 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.
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