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Abstract #0590

Non-invasive metabolic biomarkers of interneuron cell transplantation therapy in an epilepsy model

Marina Radoul1,2, Kai Qiao1,2, Donghyun Hong2, Mansi B. Parekh3, Philip Hampel3, Eric Steven Sevilla3, David Traver3, Hannah Kim3, Marina Bershteyn3, Yves Maury3, Catherine Priest3, Cory R. Nicholas3, and Myriam M. Chaumeil1,2
1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, 2Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3Neurona Therapeutics, San Francisco, CA, United States

Synopsis

Interneuron transplantation targeting GABAergic network dysfunction is a novel alternative therapeutic approach for chronic focal epilepsy. However, in vivo monitoring of response to such cellular therapeutics remains challenging. Here, we combined high resolution in vivo and ex vivo 1H MRS to investigate the metabolic alterations in epileptic hippocampus in a preclinical model of chronic mesial temporal lobe epilepsy, and the effect of human inhibitory interneuron transplantation on metabolism. We discovered that hippocampal levels of GABA, NAA/Cr, GLX/Cr, GABA/GLX and GABA/NAA were reversed to healthy control levels in epileptic mice transplanted with inhibitory interneurons, providing unique biomarkers of therapeutic response.

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Keywords