Molecular Impact of Pharmacologic Therapies on NF1 Skeletal Disease
Abstract
Localized skeletal disorders, such as fracture pseudarthroses, in children with Neurofibromatosis Type 1 (NF1) are associated with somatic loss-of-heterozygosity (LOH) at the NF1 gene locus. Such LOH events are associated with other non-skeletal manifestations of NF1, including cafe-au-lait pigment macules and plexiform neurofibromas, for example. LOH events in fracture pseudarthroses and NF1-associatedcancers are associated with dramatic increases in the activation of numerous genetic signaling pathways. These same signaling pathways are targeted by drug compounds that have been tested in clinical trials, including in children with NF1-associated cancers. Our study is testing whether these compounds can rescue the molecular dysregulation inherent in patient fracture pseudarthrosis-derived primary cells, with the goal to repurpose these compounds to treat NF1-associated fracture pseudarthrosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1212455
Entities
People
- Jonathan J. Rios
Organizations
- Scottish Rite for Children
- University of Texas at Dallas