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| http://dx.doi.org/10.1136/bmjment-2024-301025 | DOI Listing |
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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
Edith Cowan University, Perth, Western Australia, Australia.
Background: Accumulation of amyloid beta 42 (Aβ42) senile plaques is the most critical event leading to Alzheimer's disease (AD). Currently approved drugs for AD have not been able to effectively modify the disease. This has caused increasing research interests in health beneficial nutritious plant foods as viable alternative therapy to prevent or manage AD.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Washington University School of Medicine, St. Louis, MO, USA.
Background: The well-accepted statistical efficacy inference approach for Alzheimer's disease (AD) clinical trials compares the absolute difference in change from baseline at the last study visit using MMRM (henceforth referred to as MMRM-Last-Visit). Recent AD clinical trials have shown that treatment effects may be manifested prior to 18 months. The objective is to evaluate models estimating an overall treatment effect across all post-baseline visits that may characterize disease modifying effects in contemporary early AD clinical trials.
View Article and Find Full Text PDFBackground: While a number of recent anti-amyloid antibodies demonstrated a robust reduction of amyloid biomarkers in clinical trials, the impact on functional improvement is much more variable. We hypothesize that this larger variability is driven by comedications, common genotype variants and underlying tau pathology.
Method: In a previously calibrated computational neuroscience model of ADAS-Cog, we implemented the effect of soluble amyloid monomers and oligomers on glutamate and nicotinic AChR neurotransmission and the effect of intracellular tau oligomers on voltage-gated Na and K+ channels and synaptic density.
Drug Development.
Alzheimers Dement
December 2024
STEM Neurology & Neuropsychological0 Research Group Egypt (SNRGE), Port Said, Port Said, Egypt.
Background: Donepezil, an acetylcholinesterase inhibitor (AChEI), is an FDA-approved drug to treat these neurodegenerative diseases, e.g., Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI).
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