New developments in the management of achondroplasia

Wiener medizinische Wochenschrift
Wolfgang Högler, Leanne M Ward

Abstract

Achondroplasia is the most common form of disproportionate short stature. A dominantly inherited FGFR3 mutation permanently activates the fibroblast growth factor receptor 3 (FGFR3) and its downstream mitogen-activated protein kinase (MAPK) signalling pathway. This inhibits chondrocyte differentiation and puts a break on growth plate function, in addition to causing serious medical complications such as foramen magnum and spinal stenosis and upper airway narrowing. A great deal has been learned about complications and consequences of FGFR3 activation and management guidance is evolving aimed to reduce the increased mortality and morbidity in this condition, particularly deaths from spinal cord compression and sleep apnoea in infants and small children. To date, no drugs are licensed for treatment of achondroplasia. Here, we report on the various substances in the drug development pipeline which target elements in molecular disease mechanism such as FGF (fibroblast growth factor) ligands, FGFR3, MAPK signalling as well as the C‑type natriuretic peptide receptor NPR‑B (natriuretic peptide receptor B).

References

May 1, 1967·The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine·L O LangerR J Gorlin
Mar 1, 1984·The Journal of Pediatrics·R M PauliA Sommer
Sep 6, 2005·Pediatrics·Tracy L TrotterUNKNOWN American Academy of Pediatrics Committee on Genetics
Jul 17, 2007·Lancet·William A HortonJacqueline T Hecht
Sep 21, 2007·American Journal of Medical Genetics. Part a·Julia WynnJacqueline T Hecht
Oct 17, 2008·Human Molecular Genetics·Takehiko MatsushitaShunichi Murakami
Dec 4, 2012·American Journal of Human Genetics·Florence LorgetLaurence Legeai-Mallet
Jun 7, 2013·Human Molecular Genetics·Deepali N ShindeIrene Tiemann-Boege
Aug 1, 2013·Apoptosis : an International Journal on Programmed Cell Death·Kai Hung TiongChee-Onn Leong
Sep 21, 2013·Science Translational Medicine·Stéphanie GarciaElvire Gouze
Mar 29, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Kristen SimmonsJacqueline T Hecht
Sep 19, 2014·Nature·Akihiro YamashitaNoriyuki Tsumaki
Sep 24, 2015·American Journal of Medical Genetics. Part a·Klane K WhiteRavi Savarirayan
Oct 7, 2015·Nature Reviews. Endocrinology·Jeffrey BaronOla Nilsson
Apr 12, 2016·The Journal of Clinical Investigation·Davide Komla-EbriLaurence Legeai-Mallet
Aug 11, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ling JinYoshikazu Nakamura
Feb 24, 2017·Scientific Reports·Yi-Ching LeeYuan-Tsong Chen
Jun 7, 2017·Osteoarthritis and Cartilage·B FafilekP Krejci
Oct 11, 2017·The Journal of Clinical Investigation·Yugo KanaiNobuya Inagaki
May 23, 2018·Current Opinion in Pediatrics·Youn Hee JeeOla Nilsson
Jun 7, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Victoria R SandersJoel Charrow
Jul 15, 2018·Biochemical and Biophysical Research Communications·Junko HamamotoTomoko Betsuyaku
Aug 3, 2018·American Journal of Medical Genetics. Part a·Andrea MerkerLars Hagenäs
Aug 29, 2018·American Journal of Medical Genetics. Part a·Andrea MerkerLars Hagenäs
Oct 3, 2018·American Journal of Medical Genetics. Part a·S Shahrukh HashmiJacqueline T Hecht
Jan 5, 2019·Orphanet Journal of Rare Diseases·Richard M Pauli
Mar 28, 2019·Clinical Genetics·Svein O FredwallIngeborg B Lidal
Jul 4, 2019·The New England Journal of Medicine·Ravi SavarirayanJulie Hoover-Fong
Aug 11, 2019·Orphanet Journal of Rare Diseases·Stefanie WittJulia Quitmann
Nov 16, 2019·Orphanet Journal of Rare Diseases·Celine Saint-LaurentElvire Gouze

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Citations

Jul 29, 2020·The Journal of Clinical Endocrinology and Metabolism·Patrick C HanleyMichael A Levine
Feb 28, 2021·American Journal of Medical Genetics. Part a·Louise ToftsVerity Pacey
Jun 3, 2021·International Journal of Molecular Sciences·Wiktoria WrobelIwona Ben-Skowronek

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Methods Mentioned

BETA
transgenic

Clinical Trials Mentioned

NCT02055157
NCT02724228
NCT04085523

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