Tau (Tubulin-associated unit) is a microtubule-associated protein (MAP) that is primarily present in axons. Besides, Tau is a multi-functional protein. Particularly, It takes part in the cross-linking and regulation of microtubule (MT) assembly and MT stabilization. Moreover, Tau also includes modulation of axonal transport, enhancement of trophic signaling and regulation of neurite outgrowth. Additionally, Tau aggregates to form the primary constituent of neurofibrillary tangles (NFTs).

Alzheimer’s disease (AD) is the most common cause of dementia, affecting an estimated 5.8 million individuals in the United States and 50 million worldwide . While AD is characterized by the accumulation of extracellular β-amyloid (Aβ) peptide-containing plaques (amyloid plaques) and intracellular tau aggregates in the brain. So, the inhibition of tau accumulation may be a potent treatment for Alzheimer’s disease.

Semorinemab (RG 6100) is an anti-Tau humanized IgG4 monoclonal antibody.

From: Yi Guo, et al. Ageing Neur Dis 2022;2:11.

Semorinemab binds to the N terminus of tau, with the strongest binding signals observed with tau-derived peptides containing amino acids 6 to 23. Besides, Semorinemab shows a high affinity for human and recombinant cynomolgus monkey tau with K_d values of 3.8 nM and 11.2 nM, respectively. Meanwhile, Semorinemab prevents the uptake of oligomeric tau by neurons and shows neuroprotective activity in cell culture. Moreover, Semorinemab (1, 50 mg/kg, i.v., once) shows good pharmacokinetic parameters with a systemic clearance of 1.53 mL/day per kilogram and C_max concentration of 0.107 μg/g in cynomolgus monkeys. In addition, Semorinemab (3-30 mg/kg, i.p., once weekly for 13 weeks) reduces the accumulation of pathological tau; and dose-dependently decreased pTau212/214 and pTau202/205 in Tg mice with the expression of human disease-causing tau mutant (TauP301L-Tg).

All in all, Semorinemab is an anti-Tau IgG4 monoclonal antibody and has the potential for the research of Alzheimer’s Disease.

Reference:
[1] Ayalon G, et al. Sci Transl Med. 2021 May 12;13(593):eabb2639.