STEM CELLS FOR DEVELOPING NEW TREATMENT STRATEGIES

Using hiPSCs to test Lovastatin

Our latest project is developing a patient-specific platform for testing treatment strategies for Fragile X Syndrome (FXS). Recent studies from our group establish an astrocyte-specific mechanism that underlies neuronal network dysfunction in an Fmr1 knockout (FMR KO) mouse model through increased cholesterol metabolism. Lovastatin, a popular and approved medication to lower cholesterol, has been effective in remediating symptoms in FMR KO mice. Most drugs are developed using mouse models, but often fail to show efficacy in clinical trials. This project represents a new approach to tailor and test drugs on patients with diverse responses to medications. We are creating a novel human model for testing drug efficacy using astrocytes differentiated from human induced pluripotent stem cells (hiPSCs) derived from FXS and control subjects. Specifically, we are addressing lovastatin’s effectiveness in lowering astrocyte-derived cholesterol and reducing synaptotoxicity. Our results will be translated into clinical studies with FXS subjects and provide mechanistic insights into the contribution of astrocyte-derived cholesterol in synaptic deficits associated with FXS.