Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke.
A. da Silva-Candal, A. Pérez-Diaz, M. Santamaria, C. Correa-Paz, M. Rodriguez-Yanez, A. Arda, M. Perez-Mato, R. Iglesias-Rey, J. Brea, J. Azuaje, E. Sotelo, T. Sobrino, MI Loza, J. Castillo & F. Campos
Ann. Neurol. 84 260–273 (2018)
Blood/brain-glutamate grabbing is an emerging concept in the treatment of ischemic stroke, where essentially the deleterious effects of glutamate after ischemia are ameliorated by coaxing glutamate to enter the bloodstream and thus reducing its concentration in the brain.
The authors aim to demonstrate the clinical efficacy of blood glutamate grabbers in patients with stroke, and in this study a drug-repositioning strategy for the discovery of new glutamate-grabbing drugs was applied.
Riboflavin, present in the Prestwick Chemical Library®, was identified as the main hit compound during an HTS campaign, and it was further confirmed in ischemic animal models that blood glutamate was reduced as well as infarct size. These results led to a randomized double-blind phase II-b clinical trial with patients hospitalized for acute stroke. This proof of concept clinical trial showed for the first time a reliable human demonstration of the efficacy of glutamate grabbers on blood glutamate reduction in patients.