Current Status of Clinical Trials on Tau Immunotherapies.
Abstract
Tau immunotherapies have advanced from proof-of-concept studies to over a dozen clinical trials for Alzheimer's disease (AD) and other tauopathies. Mechanistic studies in animal and culture models have provided valuable insight into how these therapies may work but multiple pathways are likely involved. Different groups have emphasized the importance of intracellular vs extracellular antibody-mediated clearance of the tau protein and there is no consensus on which pool of tau should ideally be targeted. Likewise, various normal and disease-selective epitopes are being targeted, and the antibody isotypes either favor phagocytosis of the tau-antibody complex or are neutral in that aspect. Most of the clinical trials are in early stages, thus their efficacy is not yet known, but all have been without any major adverse effects and some have reported target engagement. A few have been discontinued. One in phase I, presumably because of a poor pharmacokinetic profile, and three in phase II for a lack of efficacy although this trial stage is not well powered for efficacy measures. In these phase II studies, trials with two antibodies in patients with progressive supranuclear palsy or other primary tauopathies were halted but are conti...Continue Reading
References
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
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