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Current Approaches in the Development of Molecular and Pharmacological Therapies in Craniosynostosis Utilizing Animal

Martin Rachwalski1,2,3,4, Roman H Khonsari1,3,4, Giovanna Paternoster2,4

  • 1Imagine Institute of Genetic Diseases, INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Departments of Malades, Paris, France.

Molecular Syndromology
|April 13, 2019
PubMed

Insights

Craniosynostosis, premature suture fusion, causes skull deformities. This review explores molecular and pharmacological treatments, including tyrosine kinase inhibitors, as potential alternatives to risky infant surgery.

Area of Science:

  • Craniofacial development and skeletal biology.
  • Developmental biology and genetics.
  • Surgical and regenerative medicine.

Background:

  • Cranial sutures regulate skull morphogenesis and growth.
  • Craniosynostosis results from premature suture obliteration, causing skull deformities and potential CNS issues.
  • Current surgical treatments carry significant infant morbidity risks.

Purpose of the Study:

  • To review molecular and pharmacological treatments for craniosynostosis.
  • To evaluate the potential of non-surgical strategies for craniosynostosis treatment.
  • To focus on tyrosine kinase inhibitors as a therapeutic approach.

Main Methods:

  • Review of in vitro and in vivo studies on craniosynostosis treatments.
  • Analysis of genetic factors, including FGFR and TWIST1 mutations.
  • Exploration of animal models for therapeutic development.

Main Results:

  • Gain-of-function mutations in FGFR1-3 and TWIST1 are implicated in syndromic craniosynostosis.
  • Animal models are crucial for understanding gene function in cranial sutures.
  • Various molecular and pharmacological strategies have shown promise in preclinical studies.

Conclusions:

  • Non-surgical approaches are being developed to mitigate risks associated with craniosynostosis surgery.
  • Tyrosine kinase inhibitors represent a promising pharmacological avenue for craniosynostosis treatment.
  • Further research is needed to translate these findings into safe and effective human therapies.
Keywords:
Cranial sutureCraniosynostosisFGFR2Molecular therapyTyrosine kinase inhibitors

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