Abstract
Anti-tau immunotherapies targeting phospho-epitopes have shown promising outcome in pre-clinical studies, although, with certain limitations in terms of mode of antibody delivery and concentration of antibodies required to obtain positive outcome.
Highlights
Tauopathies are a class of neurodegenerative disorders [1] which include progressive supranuclear palsy, fronto temporal dementia, Alzheimer’s disease (AD), etc
These results suggest the merits of SLB-Ab in improving spatial memory as reflected by far lesser number of SLB-Ab injections required to observe the therapeutic effect
Tauopathies are characterized by accumulation of neurofibrillary tangles (NFT) inside the cell which are composed of abnormally hyperphosphorylated microtubule-associated protein tau (MAPT) or tau protein
Summary
Virus-like particles containing 180 binding sites for antibodies per particle was chosen as the antibody delivery tool. Antibodies against phospho-tau-peptide (sequence 50-71 AA) phosphorylated at S68, T69, and T71 were coated onto chimeric Sesbania mosaic virus-like nanoparticles containing B domain from S. aureus (SLB). SLB bound antibodies showed enhanced binding to tau protein as compared to unconjugated antibodies. Passive immunization studies were conducted in okadaic acid (OKA) induced tauopathy model rats. In Barnes maze task, SLB-Ab treated rats exhibited marked learning ability in comparison to OKA rats, with progressive decrease in the number of errors made and the time taken in reaching the escape hole
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