‘Amytrapper’, a Novel Immobilized Sepharose API Matrix, Removes Amyloid-β from Circulation in vitro
| Autor: | Pazhani Sundaram, Omkar Gandbhir |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Research Report
Amyloid Peptide Matrix (biology) amyloid-β peptides law.invention Alzheimer’s therapy Sepharose 03 medical and health sciences 0302 clinical medicine law Amytrapper 030304 developmental biology chemistry.chemical_classification 0303 health sciences extracorporeal General Neuroscience amyloid In vitro Psychiatry and Mental health Clinical Psychology plasmapheresis Biochemistry chemistry Biotinylation Click chemistry Recombinant DNA Geriatrics and Gerontology Alzheimer’s disease 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease Reports |
| ISSN: | 2542-4823 |
| Popis: | 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 Aβ42. Additional testing performed on Amytrapper with sera and plasma containing Aβ42 showed retention of Aβ42 upon increasing concentrations of biotinylated Aβ42 (bio-Aβ42). Specificity of this binding was confirmed via 1) pre-blocking Amytrapper with cold (unbiotinylated) Aβ42 followed by binding experiment with biotinylated Aβ42, 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 Aβ42 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. |
| Databáze: | OpenAIRE |
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