Targeting GNAS-Driven Pathway for Precision Therapy of Fibrous Dysplasia
Awardee: J. Silvio Gutkind
Institution: University of California, San Diego
Grant Amount: $80,468.00
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Fibrous dysplasia (FD) is a rare bone disorder where normal bone is replaced with fibrous tissue, leading to deformities, fractures, and chronic pain. FD is caused by mutations in the GNAS gene, which results in the continuous activation of a signaling pathway that disrupts normal bone formation. This mutation typically occurs early in development and affects not only the skeleton but also other tissues, such as the skin and endocrine organs. Currently, there are no targeted treatments available for FD, and existing therapies are primarily focused on managing symptoms rather than addressing the underlying cause of the disease. Our research aims to better understand how FD develops by studying the stem cells that give rise to the disease and how the GNAS mutation alters their normal function. We will use advanced techniques to investigate these cells at a single-cell level, allowing us to identify the specific molecular changes that drive the progression of FD. In addition, we are exploring new therapeutic strategies by targeting key components of the GNAS signaling pathway. Specifically, we are focusing on inhibiting the PKA catalytic subunit, which is a crucial downstream player in the pathway affected by the GNAS mutation. We believe that blocking this molecule will help restore the balance of bone formation and potentially reverse the progression of FD. By combining our understanding of FD development with new therapeutic approaches, we aim to open the door to more effective treatments for patients with this debilitating condition. Our ultimate goal is to develop targeted therapies that can halt or reverse the progression of FD, improving the life expectancy and quality of life for those affected by the disease.