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FGFR3 targeting strategies for achondroplasia

Published online by Cambridge University Press:  23 April 2012

Melanie B. Laederich
Affiliation:
Shriners Hospital for Children, Research Center, Portland, OR, USA Departments of Cell & Developmental Biology and Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA
William A. Horton*
Affiliation:
Shriners Hospital for Children, Research Center, Portland, OR, USA Departments of Cell & Developmental Biology and Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA
*
*Corresponding author: William A. Horton, Research Center, Shriners Hospital for Children, 3101 SW Sam Jackson Park Road, Portland, OR 97239, USA. E-mail: wah@shcc.org

Abstract

Mutations that exaggerate signalling of the receptor tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) give rise to achondroplasia, the most common form of dwarfism in humans. Here we review the clinical features, genetic aspects and molecular pathogenesis of achondroplasia and examine several therapeutic strategies designed to target the mutant receptor or its signalling pathways, including the use of kinase inhibitors, blocking antibodies, physiologic antagonists, RNAi and chaperone inhibitors. We conclude by discussing the challenges of treating growth plate disorders in children.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2012

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References

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Further reading, resources and contacts

Little People of America (LPA), a support group for patients and parents of patients with achondroplasia and other forms of dwarfism, provides much information about the clinical management of achondroplasia as well as social and medical support for patients and their families: