miércoles, 2 de octubre de 2013

Postnatal Soluble FGFR3 Therapy Rescues Achondroplasia Symptoms and Restores Bone Growth in Mice

Postnatal Soluble FGFR3 Therapy Rescues Achondroplasia Symptoms and Restores Bone Growth in Mice

LOS PACIENTES AVANZANDO EN INVESTIGACIÓN
Iniciativas dirigidas por pacientes y acciones para fomentar la investigación de las enfermedades raras
Gracias a la financiación del Téléthon francés para la identificación genética, los investigadores están desarrollando una terapia para la acondroplasia  
LOS PACIENTES AVANZANDO EN INVESTIGACIÓN
Sci Transl Med
Vol. 5, Issue 203, p. 203ra124
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006247
  • Research Article
RARE DISEASES

Postnatal Soluble FGFR3 Therapy Rescues Achondroplasia Symptoms and Restores Bone Growth in Mice

  1. Elvire Gouze1,3,*
+ Author Affiliations
  1. 1INSERM, U1065, Team 8, Mediterranean Center for Molecular Medicine, 06204 Nice, France.
  2. 2University of Paul Sabatier Toulouse III, 31062 Toulouse, France.
  3. 3University of Nice-Sophia Antipolis, 06100 Nice, France.
  4. 4UMR CNRS 7277, INSERM U1091, Valrose Biology Institute, University of Nice Sophia Antipolis, 06108 Nice, France.
  5. 5Department of Digestive Diseases, University Hospital Center of l’Archet, 06202 Nice, France.
  6. 6Department of Biology, University Hospital Center of l’Archet, 06202 Nice, France.
  7. 7INSERM, U1043, Center of Physiopathology of Toulouse Purpan, 31024 Toulouse, France.
  1. *Corresponding author. E-mail: elvire.gouze@inserm.fr

Abstract

Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3ach/+ mice—the mouse model of achondroplasia—twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3ach/+ mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.
Citation: S. Garcia, B. Dirat, T. Tognacci, N. Rochet, X. Mouska, S. Bonnafous, S. Patouraux, A. Tran, P. Gual, Y. L. Marchand-Brustel, I. Gennero, E. Gouze, Postnatal Soluble FGFR3 Therapy Rescues Achondroplasia Symptoms and Restores Bone Growth in Mice. Sci. Transl. Med. 5, 203ra124 (2013).

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