UCLA researchers from the Department of Orthopedic Surgery, OBGYN, and Human Genetics have identified the drug infigratinib as a potential therapeutic to treat osteogenesis imperfecta (OI).
BACKGROUND: Osteogenesis Imperfecta (OI) is a heterogeneous genetic condition that can be characterized by brittle bones, recurrent fractures, and short stature. Current treatment options include medications that help increase bone density and orthopedic surgeries to correct bone deformities. However, the medications used to treat OI do not fully restore the normal structure of the growth plate—the layer of cartilage cells responsible for bone lengthening during development. Therefore, there is a demand for better therapies to treat patients with OI.
In a recent phase II clinical trial, infigratinib significantly increased the annual growth rate in children with achondroplasia, a common form of dwarfism; however, it has not yet been evaluated in other genetic bone disorders such as OI.
INNOVATION: Researchers at UCLA have treated a mouse model of moderate to severe OI with infigratinib, which targets the dysregulated fibroblast growth factor receptor signaling pathway. Treatment resulted in partial restoration of key disease features. UCLA researchers assessed the effects of treatment using femoral radiography, micro-CT imaging, and histological analysis of growth plate length. They found that femur lengths of infigratinib-treated female mice were longer. In addition, they discovered that infigratinib treatment increased growth plate lengths in both sexes, increasing long bone linear growth primarily through the proliferative zone length in the growth plate. Altogether, UCLA researchers demonstrated that inhibiting the FGFR signaling pathway with infigratinib restored growth plate morphology and improved linear growth. This discovery shows that infigratinib may be a promising therapeutic to treat features of OI.
POTENTIAL APPLICATIONS:
- Treatment of OI
- Treatment of other skeletal diseases such as Thanatophoric Dysplasia
ADVANTAGES:
- Infigratinib is FDA-approved for the treatment of bile duct cancer
- Infigratinib is orally administered
DEVELOPMENT-TO-DATE: UCLA researchers have tested infigratinib in an in vivo mouse model of OI and have shown its efficiency through various ex vivo functional assays.
Keywords: Infigratinib, osteogenesis imperfecta, growth plate, achondroplasia, fibroblast growth factor receptor, femoral radiography, micro-CT imaging, histological analysis, bone linear growth, proliferative zone length