Chhipa Rishi Raj, Gandbhir Omkar, Le Hao, Sankar Sadhana, Sundaram Pazhani
Recombinant Technologies LLC, 1090 Meriden Waterbury Turnpike, Suite 1, Cheshire, Connecticut 06410, USA.
HSOA J Alzheimers Neurodegener Dis. 2021;7(1). doi: 10.24966/and-9608/100055. Epub 2021 Oct 6.
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) . 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.
阿尔茨海默病(AD)是痴呆最常见的病因,其特征是大脑中存在β淀粉样蛋白(Aβ)斑块沉积。我们之前开发了AmyTrap肽(活性药物成分,API),并通过点击化学将其与琼脂糖珠基质相连,形成AmyTrapper基质,该基质能够从添加了生物素化Aβ42(bio-Aβ42)的人血清和血浆中结合并去除Aβ。为了拓展先前研究的思路,本研究调查了包被在具有医学可行性的聚碳酸酯导管内的AmyTrap肽(AmyTrapper导管)是否能够从人血清中结合并保留Aβ。AmyTrapper基质和新型AmyTrapper导管能够从人血清中结合并保留添加的bio-Aβ42,或从AD患者血浆中结合并保留天然Aβ。本研究还评估并展示了AmyTrapper导管的其他特性。此处呈现的结果首次提供了原理证明,即体外AmyTrapper装置有助于清除天然Aβ(来自AD患者血浆)。因此,我们的AmyTrapper装置,无论是琼脂糖基质形式还是导管形式,都可能成为一种从AD患者循环中去除Aβ的新型治疗策略。