DOCK 5: new compounds to treat pathologies related to bone loss (hyperresorption).

Development of new compounds to treat pathologies related to bone loss (hyperresorption).

CONTEXT

Osteolysis is the degradation of bone tissue. It is a disorder that may be physiological or pathological. Different types of cells are responsible for bone remodeling:

- Osteoclasts dissolve old or weakened bone matrix and eliminate it.

- Osteoblasts replace it with new bone matrix.

Current treatments for osteolytic diseases (bisphosphonates and Denosumab) cause osteoclast apoptosis, and Denosumab blocks their differentiation. A secondary loss of bone formation is then observed. The approach suggested by the DOCK 5 project is to target osteoclastic activity, but not their differentiation or their survival, thereby providing a means to avoid this problem.

BENEFITS

The DOCK 5 project focuses on developing new compounds to treat osteolytical diseases. More specifically, these compounds inhibit Rac activation by Dock5, thereby blocking osteoclastic activity without destroying it, while at the same time blocking pathological bone degradation. Applications are related to the treatment of osteolytical diseases: post-menopause osteoporosis, bone metastases, and inflammatory osteolysis such as rheumatoid polyarthritis.

The project team has demonstrated the efficiency of Dock5 inhibitors in murine models for all three of these conditions. The selected inhibitors offer the advantage of not causing a secondary blocking of bone formation, as they do not eliminate osteoclasts, unlike existing treatments.

In the context of the DOCK 5 project, the team will focus its priorities on osteoporosis and bone metastases, topics for which the stakes are significant and a true joint development strategy is possible.

APPLICATIONS

Health, osteolytical diseases (post-menopause osteoporosis, bone metastases, and inflammatory osteolysis such as rheumatoid polyarthritis).

Osteoclasts

Osteoblasts

Skeletal renewal and distribution

Balanced bone remodeling

Osteoporosis

Osteoclasts