Alzheimer's disease (AD) is the most common cause of dementia. Amyloid-␤ (A␤ 42) is implicated in AD pathogenesis. We have designed a non-immune based proprietary therapeutic, called Amytrap, a conjugate containing a retro-inverso peptide, polyethylene glycol, and human serum albumin. Amytrap not only binds A␤ 42 but also prevents and dissociates aggregated A␤ 42. Amytrap binds to the region in A␤ 42 known to trigger its self-aggregation, thus disrupting aggregation. we have obtained proof of concept on AmyTrap in a clinically relevant mouse model, namely, AD-APPSWE/Tg2576. We synthesized and characterized Amytrap and confirmed its authenticity. Efficacy evaluations were performed on young (5 months) and old (9 months) model mice. Amytrap was injected biweekly for a period of five months. Pharmacokinetics and safety toxicology were assessed in normal mice and rats, respectively. Post treatment, younger mice showed significant improvements in cognition and A␤ 42 levels in plasma, brain, and cerebrospinal fluid, while older mice showed less significant benefits. Immunohistochemistry of brain sections showed similar differences between young and old mice. They all had diminished size and number of plaques in the brain of Amytrap-treated mice. Further, treated mice did not develop antibodies to Amytrap, suggesting Amytrap is non-immunogenic. Safety toxicological studies in rats showed that Amytrap was well tolerated and therefore safe (even at 50 X the efficacy dose). Stability tests showed Amytrap is stable at 4 • C for up to one year. Efficacy and safety features make Amytrap a promising candidate for treating or modulating AD.

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.

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Alzheimer’s disease (AD) is the most common cause of dementia, characterized by the deposition of Amyloid-beta (Aβ) plaques in the brain. We have previously developed Amytrap peptide (the active pharmacological ingredient, API) and linked it to a sepharose bead matrix by click chemistry to form Amytrapper matrix, which was able to bind and remove Aβ from human sera and plasma spiked with biotinylated Aβ42 (bio-Aβ42) in vitro . To extend the logic of the previous studies, the current study investigates whether the Amytrap peptide coated inside a medically viable polycarbonate catheter (Amytrapper catheter) could bind and retain Aβ from the human sera. The Amytrapper matrix and the novel Amytrapper catheter were able to bind and retain spiked bio-Aβ42 from human sera or native Aβ from plasma of AD patients. Additional characteristics of the Amytrapper catheter are evaluated and presented in this study. The results presented here provide a proof-of-principle for the first time that extracorporeal Amytrapper device aids clearance of native Aβ (from plasma of AD patients). Thus, our device Amytrapper, either in the form of Sepharose matrix or catheter, could become a novel therapeutic strategy to remove Aβ from circulation in AD patients.