Anti-fibroblast growth factor 23 antibody therapy.
OBJECTIVE
The review is intended to provide an update on the expanding knowledge regarding diseases caused by the excess actions of fibroblast growth factor 23 (FGF23) and also on the new therapeutic measures for these diseases, with an emphasis on the anti-FGF23 antibody.


RESULTS
FGF23 decreases serum phosphate and 1,25-dihydroxyvitamin D levels. After the cloning of FGF23, several hypophosphatemic diseases, including tumor-induced osteomalacia and X-linked hypophosphatemic rickets (XLHR), were shown to be caused by excess actions of FGF23. In addition, recent studies indicated that mutations in the family with sequence similarity 20, member C (FAM20C), HRAS and NRAS genes, also caused FGF23-related hypophosphatemic diseases. The inhibition of FGF23 production or activity is, theoretically, an ideal treatment for these hypophosphatemic diseases. The C-terminal fragment of FGF23, inhibitors of FGF receptor and extracellular signal-regulated kinase, and anti-FGF23 antibody were shown to inhibit FGF23 actions both in vitro and in vivo. A phase I clinical trial of anti-FGF23 antibody has shown that this antibody increases serum phosphate in patients with XLHR.


CONCLUSIONS
These recent findings confirm that FGF23 has a pivotal role in phosphate metabolism. The inhibition of FGF23 production or activity is promising as a new therapy for FGF23-related hypophosphatemic diseases. Further studies are clearly necessary to establish the clinical utility and long-term safety of these measures.
Department of Medicine, Division of Nephrology and Endocrinology, University of Tokyo Hospital, Tokyo, Japan.
Seiji
S
Fukumoto
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D047389:Casein Kinase I / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000235:genetics / Q000628:therapy; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D017674:Hypophosphatemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D007155:Immunologic Factors / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications; D010018:Osteomalacia / Q000209:etiology / Q000628:therapy; D010710:Phosphates / Q000097:blood
D061067:Antibodies, Monoclonal, Humanized; D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; D007155:Immunologic Factors; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D047389:Casein Kinase I; C524449:FAM20C protein, human