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Drug Development.
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
Background: Astrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer's disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub-types most associated with these diseases are now reported to be present during CNS cancers of several types.
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Alzheimers Dement
December 2024
School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram, Haryana, India.
Background: Parkinson's disease is an hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid-brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Filgrastim has been reported to produce anti-oxidant, anti-inflammatory and neuromodulatory actions in previous studies.
View Article and Find Full Text PDFBackground: We have previously reported the neuroprotective effects of fosgonimeton in amyloid-β (Aβ)-driven preclinical models of Alzheimer's disease (AD). Fosgonimeton is an investigational small-molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system, currently under investigation for mild-to-moderate AD (LIFT-AD; NCT04488419). Given the recent approvals of Aβ-targeting monoclonal antibodies (Aβ-mAbs) for the treatment of AD, and growing recognition that combination therapies may improve treatment outcomes, we sought to investigate the preclinical activity of fosgonimeton in the presence of Aβ-mAbs.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Center for Health + Technology, University of Rochester Medical Center, Rochester, NY, USA.
Background: In preparation for therapeutic trails involving patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), there is a need for valid, disease-specific caregiver-reported outcome (CRO) measures capable of tracking symptomatic burden in response to therapy over time. CROs are useful tools in clinical trials for individuals with AD, MCI, and dementia who are unable to self-report. In addition, CROs are accepted by the United States Food and Drug Administration to support regulatory claims.
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Alzheimers Dement
December 2024
University College London, London, United Kingdom.
Background: Mivelsiran (ALN-APP) is an investigational, intrathecally administered RNA interference therapeutic designed to lower levels of amyloid-β (Aβ) peptide, a key driver of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) pathogenesis, by reducing upstream production of amyloid precursor protein (APP). We report additional safety, pharmacodynamic, and biomarker data from the double-blind, placebo-controlled, single ascending dose part of the ongoing mivelsiran Phase 1 study (NCT05231785).
Method: Patients with early-onset AD (symptom onset <65 years of age, Clinical Dementia Rating global score 0.
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