title: FGF23-FGF Receptor/Klotho Pathway as a New Drug Target for Disorders of Bone and Mineral Metabolism.
abstract: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by bone and works by binding to Klotho-FGF receptor complex. Excessive and deficient actions of FGF23 result in hypophosphatemic and hyperphosphatemic diseases, respectively. Therefore, it is reasonable to think that modulating FGF23 activities may be a novel therapeutic measure for these diseases. Several preclinical reports indicate that the inhibition of FGF23 activities ameliorates hypophosphatemic rickets/osteomalacia caused by excessive actions of FGF23. In addition, phase I-II clinical trials of anti-FGF23 antibody in adult patients with X-linked hypophosphatemia rickets, the most prevalent cause of genetic FGF23-related hypophosphatemic rickets, indicated that the antibody enhances renal tubular phosphate reabsorption and increases serum phosphate. However, it is not known whether the inhibition of FGF23 activities actually brings clinical improvement of rickets and osteomalacia. Available data indicate that FGF23-FGF receptor/Klotho pathway can be a new drug target for disorders of phosphate and bone metabolism.
authors.affiliation: Department of Nuclear Receptor Ligands and Vitamins Research, Fujii Memorial Institute of Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima, 770-8503, Japan. fukumoto-tky@umin.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
mesh_terms: D001842:Bone and Bones / Q000378:metabolism; D055808:Drug Discovery; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D010018:Osteomalacia / Q000188:drug therapy / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D063730:Rickets, Hypophosphatemic / Q000188:drug therapy / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Antibody; Klotho; Osteomalacia; Rickets