About 10% of FTD and ALS patients of European decent carry a long repeat expansion in the gene C9orf72. The repeat region is unconventionally translated into five "dipeptide repeat proteins" (DPRs), which are essentially very long chains of two alternating amino acids. These DPRs co-aggregate in the brain of C9orf72 patients, most abundantly poly-GA (glycine-alanine). DPRs are now widely believed that DPRs play an important role in C9orf72 FTD and ALS. Although DPR proteins form intracellular aggregates, they can be transmitted from cell to cell, which makes them potentially amenable to therapy with specific antibodies. We could show that active immunization targeting poly-GA reduces the motor deficits in a C9orf72 mouse model. Since it is known that the immune response declines with age, we will test the efficacy of direct injection of specific anti-GA antibodies in several mouse models to confirm efficacy. In addition, we will further characterize and optimize the anti-GA antibodies for future use in patients. Unlike all other aggregating proteins in neurodegenerative diseases, DPR proteins are disease-specific and have no endogenous function, which makes them an attractive target for drug development for C9orf72 patients.