Alex Edwin: “Small molecule therapeutic approach for creatine transporter deficiency: creatine prodrug delivery targeting fatty acid amide hydrolase”
SHORT SUMMARY
Alex Edwin presented ongoing research from the Montine Lab at Stanford Medicine. Their work aims to develop an orally bioavailable small molecule therapeutic for Creatine Transporter Deficiency. This poster summarizes the progress that has been made in the first six months of their project.
ABSTRACT
Effective delivery of creatine or a creatine mimetic has been the goal of numerous therapeutic approaches for the treatment of Creatine Transporter Deficiency. To date, the most advanced approaches utilize ester and amide prodrug linkages for delivery of creatine across the blood brain barrier and neuronal membranes. As a result of this work, fatty acid amide hydrolase (FAAH) has been identified as a potential enzymatic target for the controlled release of creatine within neurons. FAAH is highly expressed in brain tissue and has a broad specificity for various fatty acid amide compounds. However, prodrugs that currently target FAAH tend to suffer from poor metabolic stability and low solubility, reducing their bioavailability. To address these issues, our research focuses on refining current prodrug delivery methods. We have developed two assays for the measurement of creatine release from prodrugs in human HAP1 CrT KO cell cultures and mouse CrT KO hippocampal slice cultures. With these assays, our ongoing research seeks to identify a novel orally administered creatine therapeutic which has enhanced solubility and bioavailability within the CNS.