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Drug Development.
Alzheimers Dement
December 2024
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.
Background: The vicious cycle between depression and dementia increases the risk of Alzheimer's Disease (AD) pathogenesis and pathology. This study investigates therapeutic effectiveness versus side effects and the underlying mechanisms of intranasal dantrolene nanoparticles (IDNs) to treat depression behavior and memory loss in 5XFAD mice.
Method: 5XFAD and wild-type B6SJLF1/J mice were treated with IDNs (IDN, 5 mg/kg) in Ryanodex formulation for a duration of 12 weeks.
Drug Development.
Alzheimers Dement
December 2024
School of Pharmacy, Chapman University, Irvine, CA, USA.
Background: Although novel treatments for Alzheimer's disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.
Background: This study investigates the therapeutic versus side effects of intranasal lithium chloride (LiCl) in Ryanodex formulation vehicle (RFV) to inhibit inflammation and pyroptosis and to ameliorate on cognitive dysfunction and depressive behavior in 5XFAD mice.
Method: 5XFAD and wild type (WT) B6SJLF1/J mice were treated with intranasal or oral LiCl (3 mM/kg) dissolved in RFV starting at 2 or 9 months old and the continuous treatment lasted for 12 weeks. Behavior was examined for depression, cognition, olfaction, and motor function at the ages of 5 or 12 months.
Background: Previously, we demonstrated therapeutic benefits following intraperitoneal delivery of the TGR5 agonist HY209 in 5xFAD, a transgenic mouse model of Alzheimer's Disease (AD). Given the desirability of a more acceptable administration route for prolonged AD treatment, we assessed the efficacy of HY209 via oral delivery. This study aims to elucidate the therapeutic potential of NuCerin, an oral formulation of HY209, in the aforementioned AD model, while simultaneously identifying potential blood biomarkers indicative of NuCerin's therapeutic action.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
University of Southern California, Los Angeles, CA, USA.
Background: Blood pressure (BP) management is an accessible therapeutic target for dementia prevention. BP variability (BPV) is a newer aspect of BP control recently associated with cognitive decline, dementia and Alzheimer's disease (AD), independent of traditionally targeted mean BP levels. Most of this work has relied on largely non-Hispanic White study samples in observational cohorts.
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