GENECELLTHER · Development of biotherapies for growth plate disorders
FP7 — People (Marie Curie Actions)
- Duration
- 2009-11-01 → 2013-10-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-IRG
Lines connect the coordinator with its partners.
Results in brief
Development of biotherapies for growth plate disorders
This project aimed at developing an innovative therapeutic strategy for achondroplasia, the most common form of short limb dwarfism. Children affected by this rare disease suffer from abnormal long-bone development, resulting in short stature. In the most severe cases, they can suffer from deformations of the skull and vertebrae that can lead to severe neurological and orthopedic complications. Obtained results were highly significant and the recruited researcher successfully developed and tested a recombinant protein approach restoring bone growth in transgenic mice with achondroplasia. These results describe a novel approach for restoring bone growth and suggest that it could be a potential therapy for children with achondroplasia and related disorders. An engineer and a PhD student were directly recruited from this European funding. The project also triggered the recruitment of 4 Master students and one technician. The IRG fellowship has contributed to the reintegration of the recruited researcher who was successfully recruited as a senior researcher (position) by Inserm in 2009. This is a permanent position in France, fulfilling the long term integration requirement of the IRG.
Data: CORDIS, © European Union
Project objective
Skeletal dysplasias are a diverse and heterogeneous group of hereditary disorders characterized by malformations of bone and cartilage. These conditions affect development patterns in bones of growing children, and the clinical severity ranges from mild short stature to highly disfiguring, and even to lethal forms. Their treatment is very challenging, typically with no or limited success. This proposal is designed to explore the use of gene- and stem cell-based approaches to influence bone development in growth plate disorders characterized by aberrant constitutive cellular signaling in the growth plate chondrocytes. These biotherapeutic technologies offer the unique opportunity to manipulate and influence the cells in the developing growth plate, and if successfully applied, may functionally rescue bone growth and restore normal skeletal development. In this study, we will work to gain fundamental knowledge necessary for the rational design of a therapy for achondroplasia and Noonan syndrome. In attempting to address skeletal dysplasias, we have chosen to focus on these diseases because they are caused by gain-of-function point mutations affecting intracellular signaling in growth plate chondrocytes, and there exists transgenic mouse models containing mutations identical to that found in affected patients. The following specific aims will be addressed: Aim 1- To determine the biological effects of systemic gene delivery and overexpression of sFGFR3 in Fgfr3ach/+ mice. Aim 2- To determine if overexpression of sFGFR3 or inhibition of SHP2 expression can restore growth in bones from Ptpn11D61G/+ mice in an organ culture system. Aim 3- To determine the capacity of exogenous stem cells to influence the biology of diseased growth plate in vivo. The fellowship will contribute to the reintegration of Dr. Gouze, an expert in gene and stem cell therapies for musculoskeletal disorders, in the INSERM unit of Pr. Salles, an expert in pediatric endocrinology and growth disorders
Original text from CORDIS.
Participants
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union