Research

Life Sciences & Biotechnology

Title :

Understanding the role of PIM kinases in regulating sclerostin expression, secretion and function: Hunt for an alternate target for the treatment of osteoporosis

Area of research :

Life Sciences & Biotechnology

Focus area :

Osteoporosis treatment

Principal Investigator :

Dr. Arun Kumar Trivedi, CsIR-Central Drug Research Institute, Lucknow, Uttar Pradesh

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Details

Executive Summary :

Bone homeostasis is the balance between bone formation and resorption, with osteoblasts regulating bone formation and osteoclasts responsible for resorption and bone loss. Imbalance in these cell activities leads to osteoporosis, a skeletal disorder caused by bone loss, often in postmenopausal women or older men. Current therapies for osteoporosis indirectly inhibit bone formation, but do not correct structural abnormalities. Recent studies have highlighted the role of sclerostin as a negative modulator of osteoblastic activity and bone formation. sclerostin, a 213aa protein product of the sOsT gene, acts as an extracellular inhibitor of canonical Wnt signaling through high-affinity binding to the Wnt co-receptor LRP5 or 6. Disrupting the interaction between LRP5 or 6 and sclerostin has been recognized as a therapeutic target for osteoporosis. A neutralizing antibody against sclerostin (romosozumab) has been approved by the U.s. FDA for the treatment of osteoporosis patients with high fracture risk. Understanding the mechanism of sclerostin's regulation could shed light on the pathogenesis and treatment of metabolic bone diseases like osteoporosis.

Total Budget (INR):

45,58,600

Organizations involved