Author:
Högler Wolfgang,Ward Leanne M.
Abstract
SummaryAchondroplasia 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).
Funder
Johannes Kepler University Linz
Publisher
Springer Science and Business Media LLC
Reference48 articles.
1. Chagin AS, Newton PT. Postnatal skeletal growth is driven by the epiphyseal stem cell niche: potential implications to pediatrics. Pediatr Res. 2019; https://doi.org/10.1038/s41390-019-0722-z.
2. Baron J, Savendahl L, De Luca F, Dauber A, Phillip M, Wit JM, et al. Short and tall stature: a new paradigm emerges. Nat Rev Endocrinol. 2015;11(12):735–46.
3. Gardner M, Scerbak T, Sandberg DE. Psychosocial aspects of short stature and rhGH treatment: implicit trends over 60+ years. Pediatr Endocrinol Rev. 2018;16(Suppl 1):129–41.
4. Witt S, Kolb B, Bloemeke J, Mohnike K, Bullinger M, Quitmann J. Quality of life of children with achondroplasia and their parents—a German cross-sectional study. Orphanet J Rare Dis. 2019;14(1):194.
5. Jee YH, Baron J, Nilsson O. New developments in the genetic diagnosis of short stature. Curr Opin Pediatr. 2018;30(4):541–7.
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