Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders: Evaluation by in vitro probe acylcarnitine assay

Seiji Yamaguchi, Hong Li, Jamiyan Purevsuren, Kenji Yamada, Midori Furui, Tomoo Takahashi, Yuichi Mushimoto, Hironori Kobayashi, Yuki Hasegawa, Takeshi Taketani, Toshiyuki Fukao, Seiji Fukuda

Research output: Contribution to journalArticle

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Abstract

Background: The number of patients with mitochondrial fatty acid oxidation (FAO) disorders is recently becoming larger with the spread of newborn mass screening. Despite the advances in metabolic and molecular characterization of FAO disorders, the therapeutic studies are still limited. It was reported recently that bezafibrate (BEZ), an agonist of peroxisome proliferating activator receptor (PPAR), can restore FAO activity in cells from carnitine palmitoyltransferase-2 (CPT2) and very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies as well as clinical symptoms in the adult patients. Methods: In this study, the therapeutic effect of BEZ was determined by in vitro probe acylcarnitine (IVP) assay using cultured fibroblasts and tandem mass spectrometry on various FAO disorders. The clinical trial of BEZ treatment for a boy with the intermediate form of glutaric acidemia type 2 (GA2) was also performed. Results: The effect of BEZ was proven in cells from various FAO disorders including GA2, deficiencies of VLCAD, medium-chain acyl-CoA dehydrogenase, CPT2, carnitine acylcarnitine translocase and trifunctional protein, by the IVP assay. The aberrantly elevated long- or medium-chain acylcarnitines that are characteristic for each FAO disorder were clearly corrected by the presence of BEZ (0.4. mmol/L) in culture medium. Moreover, daily administration of BEZ in a 2-year-old boy with GA2 dramatically improved his motor and cognitive skills, accompanied by sustained reduction of C4, C8, C10 and C12 acylcarnitines in blood, and normalized the urinary organic acid profile. No major adverse effects have been observed. Conclusion: These results indicate that BEZ could be a new treatment option for FAO disorders.

Original languageEnglish
Pages (from-to)87-91
Number of pages5
JournalMolecular Genetics and Metabolism
Volume107
Issue number1-2
DOIs
Publication statusPublished - Sep 1 2012

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Bezafibrate
Assays
Fatty Acids
Multiple Acyl Coenzyme A Dehydrogenase Deficiency
Oxidation
Long-Chain Acyl-CoA Dehydrogenase
Carnitine O-Palmitoyltransferase
Therapeutics
Carnitine Acyltransferases
Acyl-CoA Dehydrogenase
Mass Screening
Motor Skills
Peroxisomes
Organic acids
Therapeutic Uses
Fibroblasts
Tandem Mass Spectrometry
acylcarnitine
In Vitro Techniques
Mass spectrometry

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders : Evaluation by in vitro probe acylcarnitine assay. / Yamaguchi, Seiji; Li, Hong; Purevsuren, Jamiyan; Yamada, Kenji; Furui, Midori; Takahashi, Tomoo; Mushimoto, Yuichi; Kobayashi, Hironori; Hasegawa, Yuki; Taketani, Takeshi; Fukao, Toshiyuki; Fukuda, Seiji.

In: Molecular Genetics and Metabolism, Vol. 107, No. 1-2, 01.09.2012, p. 87-91.

Research output: Contribution to journalArticle

Yamaguchi, S, Li, H, Purevsuren, J, Yamada, K, Furui, M, Takahashi, T, Mushimoto, Y, Kobayashi, H, Hasegawa, Y, Taketani, T, Fukao, T & Fukuda, S 2012, 'Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders: Evaluation by in vitro probe acylcarnitine assay', Molecular Genetics and Metabolism, vol. 107, no. 1-2, pp. 87-91. https://doi.org/10.1016/j.ymgme.2012.07.004
Yamaguchi, Seiji ; Li, Hong ; Purevsuren, Jamiyan ; Yamada, Kenji ; Furui, Midori ; Takahashi, Tomoo ; Mushimoto, Yuichi ; Kobayashi, Hironori ; Hasegawa, Yuki ; Taketani, Takeshi ; Fukao, Toshiyuki ; Fukuda, Seiji. / Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders : Evaluation by in vitro probe acylcarnitine assay. In: Molecular Genetics and Metabolism. 2012 ; Vol. 107, No. 1-2. pp. 87-91.
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