Advantages
- FOP is an incurable genetic disease caused by a single genetic mutation and is difficult to treat.
- The present invention provides a new therapeutic target molecule/pathway that is different from the conventional BMP-ALK2 pathway.
- Possible to reposition approved drugs or develop new drugs.
- Assays using iPS cells derived from FOP patients are possible.
Background and Technology
| FOP is a genetic disease, and the muscles and surrounding membranes, tendons, and ligaments throughout the body gradually harden and turn into bones (heterotopic ossification) triggered by the trauma in childhood., the range of movement of the joints of the limbs becomes narrower, and the back becomes deformed. The cause of FOP is constant activation of bone formation signals due to genetic mutations in ALK2, the receptor for the osteoinductive factor BMP. Steroids, nonsteroidal anti-inflammatory drugs, bisphosphonates, and the like are used as drugs to prevent the progression of ectopic ossification, but they cannot be said to be effective. Recently, a new retinoic acid receptor γ agonist has been approved by the FDA, and anti-activin antibodies and ALK2 inhibitors that inhibit the BMP-ALK2 pathway are under clinical development. However, since the BMP-ALK2 pathway is necessary for normal bone formation, there are concerns about side effects. As a result of establishing and studying iPS cells from skin fibroblasts derived from FOP patients, we elucidated the mechanism of ectopic ossification triggered by trauma and discovered a new therapeutic target pathway. We demonstrated in vitro and in vivo that heterotopic ossification is suppressed by inhibiting this pathway/target molecule. |
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Reference and Patent
- International Patent Application: WO2017/086385
Principal Investigator
Takumi ERA, Professor (Kumamoto University Institute of Molecular Embryology and Genetics)
Current Stage and Next Step
- In a teratoma ossification progression model mouse in which iPS cells derived from FOP patient skin fibroblasts were transplanted into the testes of immunodeficient mice, we demonstrated that ossification progression was suppressed by inhibiting the therapeutic target molecule or knocking it down with siRNA. (Figure)
- Technology evaluation and feasibility studies are possible through CDA/MTA/joint research.
- We are looking for partner companies to develop new drugs or reposition existing drugs.
Project No.BK-03450