A Harvard Medical School study demonstrates that a humanized monoclonal antibody (TBL-100; TAU BIOLOGIC Corporation, New York, NY) targets C-terminally truncated tau (tauC3) for the treatment of Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP).
The study (“Characterization of TauC3 antibody and demonstration of its potential to block tau propogation,” Nicholls et al., 2017; PLoS ONE 12(5): e0177914) showed the antibody’s potential to block tau in patients with Alzheimer’s disease.
TauC3, which causes intracellular neurotoxicity and is believed to be the major force behind tau propagation, exists in lower abundance than full-length tau (FLT) or N-terminally truncated tau but exerts significant pathological effects. TauC3 has the highest propensity to aggregate among all forms of tau.
The antibody has an affinity for tauC3 of 13pM (about 100-fold higher than most therapeutic antibodies have for their targets) and a specificity that is 1000-fold greater than for FLT. These factors are expected to translate into improved efficacy and safety compared to other tau antibodies in development.
"Successful humanization marks an important milestone in the development of TBL-100, which we believe offers several advantages compared to other anti-tau antibodies and small molecule tau treatments in development, both in terms of safety and improved efficacy," said Daniel G. Chain, PhD, president and CEO, TAU BIO-LOGIC. "We aim to rapidly advance this promising disease-modifying therapeutic agent for patients suffering from AD and PSP since these conditions currently lack effective therapies.”