{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Research Centre for Medical Genetics, Moscow 115522, Russia."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ekaterina Kondrateva",
      "orcid": "0000-0003-0770-2569"
    },
    {
      "affs": [
        0
      ],
      "name": "Svetlana Smirnikhina"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ewmkzkzv46s4x.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198571",
  "fulltext_url": "https://europepmc.org/articles/PMC13664941",
  "id": "ewmkzkzv46s4x",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883818",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Connective tissue disorders research"
    ]
  ],
  "openalex": "W7214363998",
  "pdf_url": "https://europepmc.org/articles/PMC13664941?pdf=render",
  "pmcid": "PMC13664941",
  "pmid": "42883818",
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ewmkzkzv46s4x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883818",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883818"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Connective tissue disorders research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Achondroplasia: Current Disease-Modifying Therapies and Genome Editing Strategies.",
  "title_text": "Achondroplasia: Current Disease-Modifying Therapies and Genome Editing Strategies.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/ewmkzkzv46s4x",
  "venue": "International journal of molecular sciences",
  "versions": []
}