‘Amytrapper’, a Novel Immobilized Sepharose API Matrix, Removes Amyloid-β from Circulation in vitro

Alzheimer’s disease (AD) is the most common cause of dementia among elderly patients afflicted by neurodegenerative diseases, caused by the accumulation of amyloid-β (Aβ). Therapeutic interventions in targeting and restricting Aβ production resulted in little or no success. However, recent studies have shown signs of success in validating Aβ as a target. Recombinant Technologies LLC (RTL) has developed and studied its proprietary Amytrap peptide to remove Aβ from circulation which in turn depletes brain Aβ in a clinically relevant mouse model of AD. In the current study, this Amytrap peptide (the active pharmacological ingredient, API) has been linked to sepharose matrix by click chemistry. The derivative namely ‘Amytrapper’ was confirmed to remove Aβ from the surrounding media spiked with Aβ(42). Additional testing performed on Amytrapper with sera and plasma containing Aβ(42) showed retention of Aβ(42) upon increasing concentrations of biotinylated Aβ(42) (bio-Aβ(42)). Specificity of this binding was confirmed via 1) pre-blocking Amytrapper with cold (unbiotinylated) Aβ(42) followed by binding experiment with biotinylated Aβ(42), 2) 2-dimensional SDS-PAGE analyses on samples harvested before and after the binding experiment, and 3) reconciling the amounts bound to beads and left over in the flow through. The results provide a proof of concept for our proposed prototype design for an Amytrapper device. The results suggest that extracorporeal clearance of Aβ(42) by Amytrapper could be a way to manage accumulation of amyloid in AD and thus could become an added mode of therapy for disease modification.