Targeting mTOR signaling to improve neurologic outcomes in MSUD
Awardee: Rebecca Ahrens-Nicklas
Institution: The Children's Hospital of Philadelphia and The University of Pennsylvania
Grant Amount:
Funding Period: February 1, 2022 - January 31, 2023
Summary:
Maple Syrup Urine Disease arises from a defect in branched chain amino acid metabolism (BCAA), that leads to toxic increases in certain amino acids throughout the body. Dietary therapy and liver transplantation can improve levels of BCAAs; however, unfortunately, patients still have neurocognitive and psychiatric symptoms. Based on work in a mouse model of MSUD, we believe that an inability to use BCAAs as fuel in the brain changes mTOR signaling, an important pathway for neurodevelopment. Other disorders with abnormal mTOR activation are known to result in learning difficulties and psychiatric symptoms. In this application, we plan to study how abnormal mTOR signaling affects the brain in MSUD and to explore new therapeutic approaches aimed at correcting this difference.