Federal Grant Award Summary

The University of Georgia Research Foundation, Inc. received a $415,250 Project Grant award from the National Center for Advancing Translational Sciences (NCATS), CFDA 93.350, effective May 1, 2026, through April 30, 2028. This award funds research to repurpose the clinically approved phosphatidylinositol 3-kinase alpha (PI3KA) inhibitor alpelisib (BYL-719) as a therapeutic treatment for Multiple Hereditary Exostoses (MHE), a rare autosomal dominant genetic disorder affecting approximately one in 50,000 children worldwide. The primary deliverable is translational research establishing the therapeutic efficacy of alpelisib in upregulating exostosin (EXT) gene expression and restoring heparan sulfate (HS) levels, which are deficient in MHE patients due to loss-of-function mutations in EXT1 or EXT2 genes. This drug repurposing approach aims to prevent or slow disease progression and reduce the formation of cartilage-capped bone tumors (exostoses) that cause skeletal deformities, chronic pain, growth retardation, and malignant transformation in approximately 5 percent of patients.

The research addresses a significant clinical gap, as currently no approved pharmacological treatments exist for MHE beyond surgical intervention and pain management. By leveraging NCATS' translational science mission to accelerate the movement of research discoveries into clinical health solutions, this project advances the translational pipeline from preclinical proof-of-concept through potential clinical trial readiness for a rare disease therapeutic intervention. The work builds on prior drug screening data identifying alpelisib's potential to restore HS homeostasis at the growth plate, thereby establishing the scientific rationale for clinical development of this repurposed therapeutic approach.