Repurposing 4-phenylbutyrate as new treatment for osteogenesis imperfecta.
| Reference number | |
| Coordinator | Karolinska Institutet - Karolinska Institutet, Institutionen för klinisk vetenskap, intervention och teknik |
| Funding from Vinnova | SEK 2 999 418 |
| Project duration | January 2026 - December 2028 |
| Status | Ongoing |
| Venture | European Joint Programme on Rare Diseases |
| Call | International collaborations with preclinical therapy studies of rare diseases |
Purpose and goal
The aim is to evaluate the drug RAVICTI/4PBA, already approved for other diseases, as a treatment for brittle bone disease (Osteogenesis Imperfecta) through drug repurposing. The goal is to elucidate the drug’s effects on cellular and tissue function, particularly bone, as well as on the secretion of type I collagen. Furthermore, the project seeks to identify mechanisms of action, such as reduced cellular stress, in cell and animal models. This will enable rapid translation to clinical trials.
Expected effects and result
The project will determine to what extent and through which mechanisms RAVICTI/4PBA reduces cellular stress, restores cellular homeostasis, and improves type I collagen secretion and bone quality in Osteogenesis Imperfecta. The study is expected to identify mechanisms of action, optimal dosing, and biomarkers of treatment response, and to generate a solid foundation for future clinical trials. The results may also have broader relevance for other diseases.
Planned approach and implementation
The project is carried out in a multidisciplinary collaboration with 6 partners and 4 work packages. The effects of RAVICTI/4PBA will be evaluated in 2 OI mouse models with respect to bone properties, biomarkers and pain. In parallel, cellular effects and molecular mechanisms will be studied in patient-derived 2D and 3D cell models. The results will be integrated to identify biomarkers and optimal dosing and to prepare a clinical trial in collaboration with clinical and regulatory partners.