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• W2895864894 abstract "Given the independent correlation of cerebral amyloid angiopathy (CAA) severity with cognitive impairment, as well as the importance of CAA linked complications in current immunotherapy trials, development of treatments to ameliorate CAA without toxicity is a critical goal. The potential translatability to humans is enhanced by testing a promising treatment in non-human primates (NHP), which are a more proximate AD model compared to transgenic mice. Our initial findings document that stimulation of innate immunity with TLR9 agonist, class B CpG ODN, is effective in reducing CAA without toxicity in an NHP model of sporadic CAA, squirrel monkey (SQM). We advanced our studies using class C CpG ODN, which has shown good safety profiles in humans and is currently being tested in clinical trials for multiple indications. Additional focus is to validate our novel MRI approach using bi-functional nanoparticles (USPIO-PEG-Aβ), in order to make this methodology suitable for monitoring the efficacy and safety of CpG ODN. In a short term study, predetermined doses of CpG ODN were subcutaneously administered in elderly female monkeys. Animals were continuously examined for signs of toxicity. Plasma taken at specific times was analyzed to identify peripheral immune responses and determine the most suitable dose for a long term study. Pre- and post-Aβ nanoprobe injection MRI scans were performed in aged monkeys to visualize the presence of microhemorrhages and Aβ deposits (CAA). Administration of CpG ODN in elderly SQMs was effective in inducing an immunostimulatory response in the absence of toxicity. No evidence of detrimental effects was observed during MRI studies in old primates, demonstrating the safety of our compound and novel MRI methodology. The R2* brain maps of pre- and post-contrast injection MRI scans were generated and subsequent region of interest-based quantitative R2* analyses in order to establish baseline CAA pathology in our aged cohorts are ongoing. Furthermore, MRI monitoring for ARIA will enhance the evaluation of CpG ODN efficacy and safety. Overall, the present study together with our earlier experimental evidence further validates the beneficial effects and safety of this innovative immunomodulatory approach, enhancing the likelihood of CpG ODN therapeutic efficacy in future clinical trials." @default.
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• W2895864894 date "2018-07-01" @default.
• W2895864894 modified "2023-10-16" @default.
• W2895864894 title "P1‐100: INNATE IMMUNITY STIMULATION VIA CLASS C CPG ODN AND MRI MONITORING OF EFFICACY AND SAFETY IN AN AGED NON‐HUMAN PRIMATE MODEL OF CAA" @default.
• W2895864894 doi "https://doi.org/10.1016/j.jalz.2018.06.102" @default.
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