Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome

Nikita Ikon, Fong-Fu Hsu, Jennifer Shearer, Trudy M. Forte, Robert O. Ryan

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Journal of Biomedical Research ›› 2018, Vol. 32 ›› Issue (2) : 107-112. DOI: 10.7555/JBR.32.20170094
Original Article

Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome

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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 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.

Keywords

mitochondria / cardiomyopathy / nanoparticles / drug delivery

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Nikita Ikon, Fong-Fu Hsu, Jennifer Shearer, Trudy M. Forte, Robert O. Ryan. Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome. Journal of Biomedical Research, 2018, 32(2): 107‒112 https://doi.org/10.7555/JBR.32.20170094

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Acknowledgments

Supported by grants from the Barth Syndrome Foundation to TF and the National Institutes of Health (R37 HL-64159) to RR. Mass spectrometry facility of Washington University is supported by NIH grants P41GM103422, P30DK020579, P30DK056341, R21HL120760. NI acknowledges receipt of a Barth Syndrome Foundation Travel Award. Parts of this work were previously presented at the 2016 Barth Syndrome Foundation Conference.

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2018 2018 by the Journal of Biomedical Research.
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