title: Sclerostin: how human mutations have helped reveal a new target for the treatment of osteoporosis.
abstract: In the 1990s there was a tremendous mood of optimism among pharmaceutical scientists that identification of disease-associated variations in the human genome would result in a surge of new drug targets (the 'gene-to-drug' mantra). To date the expected deluge of new drugs has not arrived. However, a small number of drugs arising directly from the study of rare human disorders showing Mendelian inheritance are now entering late stage clinical trials. Here we describe the advantages of this approach and discuss the background and early clinical trial findings with antibodies directed at a target identified in this way.
authors.affiliation: UCB Pharma, 216 Bath Road, Slough SL1 4EN, UK. martyn.robinson@ucb.com
authors.forename: Martyn K
authors.initials: MK
authors.lastname: Robinson
authors.forename: John
authors.initials: J
authors.lastname: Caminis
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brunkow
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D055808:Drug Discovery; D005819:Genetic Markers / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D015576:Hyperostosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009154:Mutation; D010024:Osteoporosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D013576:Syndactyly / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human