The mid-region of tau, closer to the MTBR, is an alternative target to N-terminal regions. In April 2018, researchers from UCB Biopharma described results from a seeding model in which PHFs were injected into transgenic mouse models, and antibodies that targeted the mid-domain were able to suppress aggregation, while N-terminal antibodies were not. [112] Following from these data, UCB is further developing UCB0107, a monoclonal antibody to the tau mid-domain (amino acids 235–246), which completed Phase 1 studies in December 2018 (NCT03464227). Janssen also has a mid-region antibody (JNJ-63733657) in a Phase 1 clinical trial (NCT03375697). Preclinical data showed that a UCB anti-tau antibody that recognize a mid-domain region epitope on tau, is more efficacious at blocking pathology induced by Alzheimer’s disease brain-derived material in vivo than a tau antibody which recognizes an N-terminal epitope [113].
