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Takuya Takahashi, M.D., Ph.D.

Takuya Takahashi, M.D., Ph.D.

Professor of Physiology
Graduate School of Medicine, Yokohama City University

Dr. Takuya Takahashi has a personal interest in the molecular mechanisms underlying synaptic functions and their clinical application. Dr. Takahashi has focused on AMPA receptors for over a decade. He discovered experience or learning drives AMPA receptors into synapses (Neuron 2100, PNAS, 2011, Nature communications 2013). He also found neonatal maltreatment alters synaptic AMPA receptor trafficking (J.Clinical Investigation 2012, PNAS 2016). Further, his research team developed novel techniques to inactivate AMPA receptors in vivo with chromophore-assisted light inactivation (CALI) and found that the acute inactivation of synaptic AMPA receptors in vivo with this technique erases fear memory (Nature Biotechnology 2017). While this research has been conducted with rodents using molecular and cellular biological techniques, electrophysiological approach, and imaging with two photon laser scanning microscope Dr. Takahashi became interested in the application of findings obtained from basic neuroscience on synapses to human biology to clinics. In collaboration with FUJIFILM, they found a compound, edonerpic maleate, which facilitates synaptic AMPA receptor delivery leading to the acceleration of recovery of motor function with rehabilitation after brain injury (Science 2018). The research team also identified a target protein, and target protein deficient mice failed to exhibit the acceleration of motor function recovery after brain injury with this compound. This prominent effect was also observed in primates. A clinical trial of this compound is currently being conducted. The team also developed a probe to quantify AMPA receptor density in the living human brain with positron emission tomography (PET) (Nature Medicine 2020). This probe is currently used in the clinical trial of edonerpic maleate as a biomarker for functional recovery. They are also planning to classify human psychiatric disorders, as well as neurological disorders, based on the distribution of AMPA receptors in the brain. This will provide strong molecular evidence of clinical applications of ampakines and is expected to increase the success rates of clinical trials of these drugs.