Pre-Clinical Safety and Efficacy Evaluation of Amytrap, a Novel Therapeutic to Treat Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia. Amyloid-β (Aβ(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 Aβ(42) but also prevents and dissociates aggregated Aβ(42). Amytrap binds to the region in Aβ(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 Aβ(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.