Advantages
- New treatment and prophylaxis for BRONJ, for which there has been no treatment or prophylaxis.
Background and Technology
Bisphosphonates (BPs) such as zoledronic acid (Zol) are widely used for osteoporosis and bone metastases from cancer, and BRONJ is a characteristic form of osteonecrosis of the jaw that occurs in patients receiving BPs and is a medical condition resulting from suppressed bone metabolism caused by long-term administration of these drugs. It often develops as a complication related to dental treatment and is caused by the failure of normal wound healing after oral surgery such as tooth extraction or periodontal treatment. Specific symptoms include gingival pain, swelling, exposed tooth bone, festering, decayed bone, and jaw loss. The incidence of the disease is said to be 1 to 4 in 10,000 for oral drugs and 1 to 2 in 100 for intravenous drugs. It also occurs with denosumab (an anti-RANKL monoclonal antibody preparation).
We found that Zol can cause BRONJ by inducing cellular senescence and that bone marrow-derived mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) act in an inhibitory manner against cellular senescence. Furthermore, they demonstrated that specific miRNAs specifically contained in MSCs-EVs inhibit Zol-induced cellular senescence and prevent osteonecrosis of the jaw.
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Reference and Patent
- Patent pending
Principal Investigator
Junna WATANABE, Kiyoshi SAKAI (Nagoya University Graduate School of Medicine)
Current Stage and Next Step
- Specific miRNAs suppressed Zol-induced decrease in proliferation of rat bone marrow cells and increased expression of senescence genes and others (in vitro).
- Intravenous administration of a specific miRNA and atelocollagen complex in a rat BRONJ model (Zol + tooth extraction) inhibited osteonecrosis of the jaw (n=6, in vivo, Fig.)
- Seeking partner companies to develop BRONJ therapeutic and prophylactic drugs using specific miRNAs as active ingredients.
- Since BRONJ risk (e.g., dental complications) is determined when BPs are initiated for osteoporosis patients, a possible method is to administer this drug prophylactically to high-risk patients or as a therapeutic agent early in the onset during follow-up.
Project No. BK-04341