title: Tissue and plasma globotriaosylsphingosine could be a biomarker for assessing enzyme replacement therapy for Fabry disease.
abstract: Fabry disease is a genetic disease caused by a deficiency of alpha-galactosidase A (GLA), which leads to systemic accumulation of glycolipids, predominantly globotriaosylceramide (Gb3). With the introduction and spread of enzyme replacement therapy (ERT) with recombinant GLAs for this disease, a useful biomarker for assessing the response to ERT is strongly required. We measured the tissue level of lyso-globotriaosylsphingosine (lyso-Gb3) in Fabry mice by means of high performance liquid chromatography, and compared it with the Gb3 level. The results revealed a marked increase in the lyso-Gb3 level in most tissues of Fabry mice, and which decreased after the administration of a recombinant GLA as in the case of Gb3, which is usually used as a biomarker of Fabry disease. The response was more impressive for lyso-Gb3 compared with for Gb3, especially in kidney tissues, in which a defect significantly influences the morbidity and mortality in patients with this disease. The plasma level of lyso-Gb3 also decreased after the injection of the enzyme, and it was well related to the degradation of tissue lyso-Gb3. Thus, lyso-Gb3 is expected to be a useful new biomarker for assessing the response to ERT for Fabry disease.
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Tadayasu
authors.initials: T
authors.lastname: Togawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kodama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsukimura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukushige
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000473:pathology / Q000628:therapy*; D006017:Glycolipids / Q000032:analysis* / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D051379:Mice; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage; D013107:Sphingolipids / Q000032:analysis* / Q000097:blood; D000519:alpha-Galactosidase / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D011994:Recombinant Proteins; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; D000519:alpha-Galactosidase