Advantages
- A novel therapeutic approach targeting the newly discovered pathophysiology of GIOP.
- Administration of Yoda1, a Piezo1 agonist, to a GIOP mouse model demonstrated significant improvements in bone mass and strength.
Technology Overview & Background
Glucocorticoid-induced osteoporosis (GIOP) is one of the most severe side effects of glucocorticoid therapy, commonly used to treat autoimmune and other diseases. It is reported that approximately 30-50% of patients undergoing long-term glucocorticoid therapy suffer from fractures. GIOP affects a wide age range, from children to the elderly, and unlike postmenopausal osteoporosis, fracture risk in GIOP cannot be solely predicted by bone mineral density. The detailed mechanisms of GIOP have remained unclear, and current osteoporosis treatments often fail to sufficiently prevent fractures, necessitating the development of new therapies based on deeper insights into GIOP pathology.
The researchers identified a similarity in bone structure between GIOP and disuse osteoporosis and hypothesized that patients with GIOP have impaired mechanical stress responsiveness in osteocytes. Their research revealed that reduced expression of the Piezo1 mechanosensitive calcium ion channel in osteocytes is a central factor in GIOP pathogenesis. Additionally, a comprehensive gene analysis identified Hes1 as a novel positive transcription factor for Piezo1. Administration of Yoda1, a Piezo1 agonist, restored mechanical stress responsiveness and improved bone mass and strength in GIOP model mice. These findings suggest that agents that activate Piezo1 or enhance Hes1 expression could serve as novel, more effective therapies for GIOP compared to current treatments.
Data
- Comparison of PIEZO1 expression in bone tissue of GIOP patients and non-GIOP patients revealed that PIEZO1 expression in osteocytes was significantly reduced in GIOP patients, as confirmed by immunostaining and Western blotting.
- A GIOP mouse model induced by glucocorticoid administration (dexamethasone: DEX) showed that intraperitoneal injection of Yoda1, a Piezo1 agonist, almost completely prevented bone mass and strength loss.
- In GIOP model mice, mechanical stress-induced bone mass increase was attenuated, but Yoda1 administration restored this response to levels comparable to the control group.
Publication
In progress
Patent
Applied (Unpublished)
Principal Investigator & Academic Institution
Associate Prof. Kousuke EBINA (Department of Orthopaedic Surgery, Osaka University)
Expectations
TECH MANAGE CORP. is looking for a pharmaceutical company/start-up interested in drug development based on this research project. Opportunities for collaboration include:
- Drug delivery systems (DDS) combining Piezo1 agonists with bone-targeting technology for GIOP
- Drug development involving bisphosphonate-Piezo1 agonist conjugates for GIOP treatment
- Gene therapy for GIOP targeting Hes1
- Development of novel Piezo1 agonists for GIOP therapeutics
Please contact us if you would like to discuss this invention or project further with our researchers.
Project No. TT-05050