Molecular Studies Investigating the Link Between Dendritic mRNA Translation and Repression Leading to Epilepsy in TSC

Principal Investigator: RAAB-GRAHAM, KIMBERLY
Institution Receiving Award: TEXAS, UNIVERSITY OF, AT AUSTIN
Program: TSCRP
Proposal Number: TS130081
Award Number: W81XWH-14-1-0061
Funding Mechanism: Idea Development Award - Optional Qualified Collaborator
Partnering Awards:
Award Amount: $529,223.09


Our research has focused on understanding how mammalian target of rapamycin (mTOR) kinase regulates protein synthesis and neuronal excitability. mTOR is overactive in Tuberous Sclerosis Complex (TSC) and is believed to be the root of serious symptoms associated with this disease such as epilepsy and autism. The proposed studies are designed to extend our previous findings on how a potassium channel, often referred to as a dendritic shock absorber, is reduced when mTOR is active. Our goal is to discover the exact composition of this ion channel when mTOR is inhibited, in order to design new therapies to increase its expression in TSC. Furthermore, we have also discovered that it is possible restrict mTOR activity to the dendrites using FDA approved drugs. We want to test if these drugs reduce the global increase in mTOR activity found in animal models of TSC yet allows mTOR to be active in a site specific manner in dendrites, the site of memory consolidation. These studies promise new therapeutic strategies to treat the symptoms of TSC such as epilepsy and depression. Resulting data will provide motivation for clinical studies. Since, the drugs that will be tested are already FDA approved off target uses of them should proceed faster than the development of new novel medications.