Grant: Team Grant: ERDERA Joint Transnational Call

The goal of this transnational proposal is to develop a biologic therapy that is effective for four related neurodevelopmental diseases. GRIN disorder is a life-threatening and highly disabling rare genetic disease caused by de novo variants in the heterozygous state. There are seven GRIN genes that encode a type of ionotropic glutamate receptor, the NMDA receptor, that is essential for synaptic connectivity, learning, and memory. Four of the seven genes (GRIN1, 2A, 2B, and 2D) are implicated in GRIN disorder, where a single nucleotide change has devastating consequences on cognition, behaviour, vision, speech, movement, sleep, and feeding. There are four teams that each specialized in one of the genes that cause GRIN disorder: GRIN1, GRIN2A, GRIN2B, and GRIN2D. The four teams have each developed patient-variant mouse models validated with electrophysiological and behavioural measures. In addition, each team has expertise with specific outcomes and biomarkers that will be applied to the other groups. We are using serum ELISA, transcriptomics, proteomics, cell morphology, and EEG recording analyses. We will share animals and tissues so that these specialized outcome measures are applied to the four GRIN genes and potentially developed as biomarkers for clinical trials.