[Research Articles] Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimers disease

We describe here the generation, preclinical characterization, and phase 1 clinical characterization of semorinemab, a humanized anti-tau monoclonal antibody with an immunoglobulin G4 (igG4) isotype backbone. Semorinemab binds all six human tau isoforms and protects neurons against tau oligomer neurotoxicity in cocultures of neurons and microglia. In addition, when administered intraperitoneally once weekly for 13 weeks, murine versions of semorinemab reduced the accumulation of tau pathology in a transgenic mouse model of tauopathy, independent of antibody effector function status. Semorinemab also showed clear evidence of target engagement in vivo, with increases in systemic tau concentrations observed in tau transgenic mice, nonhuman primates, and humans. Higher concentrations of systemic tau were observed after dosing in AD participants compared to healthy control participants. No concerning safety signals were observed in the phase 1 clinical trial at single doses up to 16,800 mg and multiple doses totaling 33,600 mg in a month.

Source: Science Translational Medicine - May 12, 2021 Category: Biomedical Science Authors: Ayalon, G., Lee, S.-H., Adolfsson, O., Foo-Atkins, C., Atwal, J. K., Blendstrup, M., Booler, H., Bravo, J., Brendza, R., Brunstein, F., Chan, R., Chandra, P., Couch, J. A., Datwani, A., Demeule, B., DiCara, D., Erickson, R., Ernst, J. A., Foreman, O., He, Tags: Research Articles Source Type: research