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In the Siege of Alzheimer´s Castle: Contribution to Immunotherapy
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The accumulation of amyloid-beta (Aβ) and intracellular neurofibrillary tangles (tau) in the brain are the two major neuropathological hallmarks of Alzheimer's Disease (AD). Active and passive immunotherapies have been tested for limiting cerebral Aβ deposition and/or accelerate its clearance. In such way, with our focus on AD diagnosis and therapy, we have created and characterized a bunch of antibodies targeting Aβ and tau.
The STAB-Mab was developed in 2011 with theranostic purposes, and now has been
biochemically characterized and tested in pre-clinical trials, demonstrating significant biochemical and cognitive improvements in mice AD models. The use of a number of analytical techniques, form WB to NMR, allowed us to confirm a widespread epitope centered within the first half of the Aβ peptide. This interaction allows STAB-Mab to bind several aggregated species, besides monomers and APP and to inhibit the stabilization of β-strand motifs, which could be the reason of the promising pre-clinical results.
The two minibodies derived from the STAB-Mab were designed for being significantly smaller and more versatile, however, their functionality was seriously affected, having a significantly lower affinity and being unable to stop AD pathology in mice AD models.
On the other hand, within another European Project addressing tau pathology, we have
developed a series of hybridomas producing monoclonal antibodies specifically targeting tau wearing certain post-transcriptional modifications. The most promising specific antibodies targeting acetylated and phosphorylated tau were delivered to the partners to be tested with biological and clinical samples.
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Alzheimer´s Aβ APP tau antibody immunotherapy