Functional analysis of „Gain-of-function“ variants in the GRIN-genes as precision medicine approach with Memantine

• Applicant: Ilona Krey
• Subject Area: Human Genetics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535466217

According to the published knowledge, four GRIN genes are associated with genetic disease and genotype-phenotype correlations have already been described for a few of these genes in small cohort. We know that electrophysiological analysis can provide information about the functional impairment of the NMDAR and these results are essential for further possible precision medicine approaches (LoF: L-serine, GoF: memantine). In contrast to LoF, the data on the benefit of the precision medicine approach with memantine is rare. A large number of published case report present a lack of functional clarification of the respective variant. The aim of this project proposal is to answer the question of a therapeutic benefit of NMDAR block with memantine in patients with GRIN-associated diseases due to GoF variants. For this purpose, functional analyses of published incomplete case reports will be performed and supplemented by unpublished cases from our GRIN registry. The analyses will be prepared at our long-term cooperation partner atCFERV and will be finalised by meself. I am planning a retrospective multicentre data collection and analysis of individuals with GRIN-associated disease. This project will therefore not only deepen the cooperation between our two institutions, but additionally allow mutual insights, enable an active exchange of knowledge and expand both our expertise.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Stephen Traynelis