Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome
Nikita Ikon, Fong-Fu Hsu, Jennifer Shearer, Trudy M. Forte, Robert O. Ryan
Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome
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.
mitochondria / cardiomyopathy / nanoparticles / drug delivery
[1] |
Clarke SL, Bowron A, Gonzalez IL,
Pubmed
|
[2] |
Bione S, D’Adamo P, Maestrini E,
Pubmed
|
[3] |
Whited K, Baile MG, Currier P,
Pubmed
|
[4] |
Xu Y, Malhotra A, Ren M,
Pubmed
|
[5] |
Valianpour F, Mitsakos V, Schlemmer D,
Pubmed
|
[6] |
Ikon, N and Ryan RO. Cardiolipin and mitochondrial cristae organization[J]. BBA Biomembranes, 2017, 1859: 1156–1163.
|
[7] |
Bissler JJ, Tsoras M, Göring HH,
Pubmed
|
[8] |
Ferri L, Donati MA, Funghini S,
Pubmed
|
[9] |
Ikon N, Ryan RO. Barth syndrome: connecting cardiolipin to cardiomyopathy[J]. Lipids, 2017, 52(2): 99–108
Pubmed
|
[10] |
Houtkooper RH, Vaz FM. Cardiolipin, the heart of mitochondrial metabolism[J]. Cell Mol Life Sci, 2008, 65(16): 2493–2506
Pubmed
|
[11] |
Schlame M, Ren M. Barth syndrome, a human disorder of cardiolipin metabolism[J]. FEBS Lett, 2006, 580(23): 5450–5455
Pubmed
|
[12] |
Valianpour F, Wanders RJ, Overmars H,
Pubmed
|
[13] |
Makaryan V, Kulik W, Vaz FM,
Pubmed
|
[14] |
Ryan RO. Nanodisks: hydrophobic drug delivery vehicles[J]. Expert Opin Drug Deliv, 2008, 5(3): 343–351
Pubmed
|
[15] |
Ryan RO. Nanobiotechnology applications of reconstituted high density lipoprotein[J]. J Nanobiotechnology, 2010, 8: 28
Pubmed
|
[16] |
Ikon N, Su B, Hsu FF,
Pubmed
|
[17] |
Acehan D, Vaz F, Houtkooper RH,
Pubmed
|
[18] |
Soustek MS, Falk DJ, Mah CS,
Pubmed
|
[19] |
Phoon CK, Acehan D, Schlame M,
Pubmed
|
[20] |
Ryan RO, Forte TM, Oda MN. Optimized bacterial expression of human apolipoprotein A-I[J]. Protein Expr Purif, 2003, 27(1): 98–103
Pubmed
|
[21] |
Hsu FF, Turk J, Rhoades ER,
Pubmed
|
[22] |
Hsu FF, Turk J. Characterization of cardiolipin as the sodiated ions by positive-ion electrospray ionization with multiple stage quadrupole ion-trap mass spectrometry[J]. J Am Soc Mass Spectrom, 2006, 17(8): 1146–1157
Pubmed
|
[23] |
Hsu FF, Turk J. Characterization of cardiolipin from Escherichia coli by electrospray ionization with multiple stage quadrupole ion-trap mass spectrometric analysis of [M- 2H+ Na]- ions[J]. J Am Soc Mass Spectrom, 2006, 17(3): 420–429
Pubmed
|
[24] |
Hsu FF, Turk J. Toward total structural analysis of cardiolipins: multiple-stage linear ion-trap mass spectrometry on the [M- 2H+ 3Li]+ ions[J]. J Am Soc Mass Spectrom, 2010, 21(11): 1863–1869
Pubmed
|
[25] |
Cole LK, Mejia EM, Vandel M,
Pubmed
|
/
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