We generated and characterized a monoclonal humanized
version of a select mouse antibody targeting a non-phospho-epitope located in the N-terminal region of Tau spanning aa 2–18 (Tau2-18, known as PAD, phosphatase activation domain). This part of the protein is normally hidden in a paperclip-like conformation in native (normal) protein, but becomes exposed in aggregated (bad) pathological Tau. It has been shown that exposed PAD plays an important role in the inhibition of anterograde fast axonal transport as well as in polymerization of Tau. In other words, if Tau breaks then your brain can't process information and memory.
Studies of human postmortem tissues from Alzheimer's Disease brain extracts with antibodies that only recognize the bad Tau, demonstrated that exposure of the N-terminal region of Tau is an early event in Alzheimer's Disease that becomes more and more exposed as Alzheimer's Disease progresses.
Based on the above, we expected, and found, that our antibodies generated against Tau2–18 epitope recognize pathological (bad), but not normal Tau and prevent/decrease the polymerization of this molecule.
We hired GenScript
to humanize and characterize our anti-Tau antibody. GenScript has also developed a CHO cell line of our anti-tau antibody producing >1.5 g/l of this therapeutically potent Mab. Moving from laboratory to production scale is very important. Not everybody can make such transfer without losing quality and efficacy.
The humanized antibody was termed Armanezumab according to "Programme on International Nonproprietary Names (INN), Quality Assurance and Safety: Medicines, Essential Medicines and Pharmaceutical Policies (EMP)" of WHO (World Health Organization).
Accumulation of pathological Tau in the brains correlates with dementia in Alzheimer's Disease patients. Thus, by the time clinical symptoms appear, there is already substantial Tau pathology in the brains. Therefore, we expect that anti-Tau therapy may be most effective when disease progression is more advanced.
Currently, the majority of neuroscientists agree that one of the main targets for Alzheimer's Disease is pathological forms of Tau protein. The majority of scientific data support the hypothesis that "bad" (pathological) Tau aggregation is the main significant event in Alzheimer's Disease pathogenesis and which leads to obvious cognitive changes in people's behavior.