Supported projects

O201701 – Establishment of proof of concept for the gene therapy-modified bone marrow transplant test in osteoconductive and osteolytic constitutional bone pathologies: study of cellular models

Scientific leader
Pr. Valérie Cormier-Daire

The bone is a highly specialized tissue in constant renewal, thanks to coordinated destruction and reconstruction, due to osteoclast and osteoblast cells, respectively. Constitutional bone diseases related to a problem of osteoclast function are marked either by bone condensation (loss of bone destruction) or by progressive bone lysis (excessive destruction of bone). In both cases, patients have severe pain, skeletal deformities and major functional impairment. Nowadays, these pathologies have no specific treatment, and patients generally benefit only from analgesics. Since osteoclasts are derived from bone marrow hematopoietic stem cells, bone marrow transplantation after genetic correction by gene therapy can theoretically be considered as a curative treatment. Therefore, the aim of the project is to continue the studies carried out on the cell cultures of patients with Ghosal hematodiaphyseal dysplasia syndrome (osteoconductive disease). Indeed, our team identified the gene responsible for this condition and was able to show that the imbalance of the levels of various cytokines (messenger molecules of inflammation) induces osteocondensation of patients.

A better understanding of the mechanisms linking inflammation to bone mass (either in excess or in default) will provide a better understanding of the role of osteoclasts. In the long term, these data should make it possible to argue the interest of the establishment of animal models to try the genetically corrected bone marrow transplant in these mutilating bone diseases.

Verma Subash Chand