Achondroplasia: Current Disease-Modifying Therapies and Genome Editing Strategies.
- 1Research Centre for Medical Genetics, Moscow 115522, Russia.
Abstract
Achondroplasia (ACH) is the most common non-lethal skeletal dysplasia and is caused in the vast majority of cases by a heterozygous gain-of-function variant in fibroblast growth factor receptor 3 (FGFR3, p.Gly380Arg). Hyperactive FGFR3 signaling constrains endochondral bone growth by suppressing growth-plate chondrocyte proliferation and hypertrophic differentiation. In the past decade, management has expanded beyond supportive care, and several mechanism-based interventions have shown disease-modifying effects in clinical studies. These include the activation of the NPR2/CNP axis with vosoritide and navepegritide and the pharmacologic attenuation of FGFR signaling with infigratinib, while extracellular biologics designed to modulate ligand-receptor interactions remain investigational. In parallel, gene-based approaches are increasingly discussed as routes toward the etiology-directed control of the causal driver, ranging from the cartilage-biased tuning of FGFR3 expression to variant-level genome editing concepts. Here, we synthesize the current therapeutic landscape, explicitly distinguish pathway-targeted disease modification from etiology-directed genetic strategies, and highlight the key translational barriers for gene-based approaches, including target-tissue delivery to the growth-plate, dose control and durability across development, redosing and immunogenicity constraints, and long-term safety.
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BibTeX
@article{kondrateva2026achondroplasia,
title = {{Achondroplasia: Current Disease-Modifying Therapies and Genome Editing Strategies.}},
author = {Ekaterina Kondrateva and Svetlana Smirnikhina},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198571},
url = {https://europepmc.org/article/MED/42883818},
note = {CC BY},
}
RIS
TY - JOUR
TI - Achondroplasia: Current Disease-Modifying Therapies and Genome Editing Strategies.
AU - Ekaterina Kondrateva
AU - Svetlana Smirnikhina
PY - 2026
DA - 2026/09/25
JO - International journal of molecular sciences
DO - 10.3390/ijms27198571
UR - https://europepmc.org/article/MED/42883818
AB - Achondroplasia (ACH) is the most common non-lethal skeletal dysplasia and is caused in the vast majority of cases by a heterozygous gain-of-function variant in fibroblast growth factor receptor 3 (FGFR3, p.Gly380Arg). Hyperactive FGFR3 signaling constrains endochondral bone growth by suppressing growth-plate chondrocyte proliferation and hypertrophic differentiation. In the past decade, management has expanded beyond supportive care, and several mechanism-based interventions have shown disease-modifying effects in clinical studies. These include the activation of the NPR2/CNP axis with vosoritide and navepegritide and the pharmacologic attenuation of FGFR signaling with infigratinib, while extracellular biologics designed to modulate ligand-receptor interactions remain investigational. In parallel, gene-based approaches are increasingly discussed as routes toward the etiology-directed control of the causal driver, ranging from the cartilage-biased tuning of FGFR3 expression to variant-level genome editing concepts. Here, we synthesize the current therapeutic landscape, explicitly distinguish pathway-targeted disease modification from etiology-directed genetic strategies, and highlight the key translational barriers for gene-based approaches, including target-tissue delivery to the growth-plate, dose control and durability across development, redosing and immunogenicity constraints, and long-term safety.
SN - 1422-0067
ER -