title: Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders: evaluation by in vitro probe acylcarnitine assay.
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.
  
  
  CONCLUSIONS
  These results indicate that BEZ could be a new treatment option for FAO disorders.
authors: Department of Pediatrics, Shimane University School of Medicine, Izumo, Shimane 693-8501, Japan. seijiyam@med.shimane-u.ac.jp
authors: Seiji
authors: S
authors: Yamaguchi
authors: Hong
authors: H
authors: Li
authors: Jamiyan
authors: J
authors: Purevsuren
authors: Kenji
authors: K
authors: Yamada
authors: Midori
authors: M
authors: Furui
authors: Tomoo
authors: T
authors: Takahashi
authors: Yuichi
authors: Y
authors: Mushimoto
authors: Hironori
authors: H
authors: Kobayashi
authors: Yuki
authors: Y
authors: Hasegawa
authors: Takeshi
authors: T
authors: Taketani
authors: Toshiyuki
authors: T
authors: Fukao
authors: Seiji
authors: S
authors: Fukuda
mesh_terms: D001629:Bezafibrate / Q000008:administration & dosage / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000652:urine; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism* / Q000652:urine; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D002264:Carboxylic Acids; D005227:Fatty Acids; C116917:acylcarnitine; D002331:Carnitine; D001629:Bezafibrate