ReviewCurrent Alzheimer research2018
(-)-Phenserine and Inhibiting Pre-Programmed Cell Death: In Pursuit of a Novel Intervention for Alzheimer's Disease.
Review in Current Alzheimer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06774261 (A Phase 1b Dose Range Finding Study of Phenserine Compared to Donepezil in Participants With Early or Mild Alzheimer's Disease), which is not on this map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1b Dose Range Finding Study of Phenserine Compared to Donepezil in Participants With Early or Mild Alzheimer's Disease
Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine.AAPS PharmSciTech · 2024Article
- Phytochemical Compounds and Nanoparticles as Phytochemical Delivery Systems for Alzheimer's Disease Management.Molecules (Basel, Switzerland) · 2022Review
- Article
- Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.Neuropsychiatric disease and treatment · 2021Review
- The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease.Journal of central nervous system disease · 2021Review
- Drug repositioning and repurposing for Alzheimer disease.Nature reviews. Neurology · 2020Review
- (-)-Phenserine tartrate (PhenT) as a treatment for traumatic brain injury.CNS neuroscience & therapeutics · 2020Review
- Cholinesterase inhibitors as Alzheimer's therapeutics (Review).Molecular medicine reports · 2019Review
- Canine Cognitive Dysfunction and Alzheimer's Disease - Two Facets of the Same Disease?Frontiers in neuroscience · 2019Review
- Alzheimer's Disease and Its Potential Alternative Therapeutics.Journal of Alzheimer's disease & Parkinsonism · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundConcussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities. Multiple clinical trials targeting mechanisms based on the Amyloid Hypothesis of AD have so far failed, indicating that it is prudent for new drug developments to also pursue mechanisms independent of the Amyloid Hypothesis. To address these issues, we have proposed the use of an animal model of concussion/TBI as a supplement to AD transgenic mice to provide an indication of an AD drug candidate's potential for preventing PPCD and resulting progression towards dementia in AD.
methodsWe searched PubMed/Medline and the references of identified articles for background on the neuropathological progression of AD and its implications for drug target identification, for AD clinical trial criteria used to assess disease modification outcomes, for plasma biomarkers associated with AD and concussion/TBI, neuropathologies and especially PPCD, and for methodological critiques of AD and other neuropsychiatric clinical trial methods.
resultsWe identified and address seven issues and highlight the Thal-Sano AD 'Time to Onset of Impairment' Design for possible applications in our clinical trials. Diverse and significant pathological cascades and indications of self-induced neuronal PPCD were found in concussion/TBI, anoxia, and AD animal models. To address the dearth of peripheral markers of AD and concussion/TBI brain pathologies and PPCD we evaluated Extracellular Vesicles (EVs) enriched for neuronal origin, including exosomes. In our concussion/TBI, anoxia and AD animal models we found evidence consistent with the presence of time-dependent PPCD and (-)-phenserine suppression of neuronal self-induced PPCD. We hence developed an extended controlled release formulation of (-)-phenserine to provide individualized dosing and stable therapeutic brain concentrations, to pharmacologically interrogate PPCD as a drug development target. To address the identified problems potentially putting any clinical trial at risk of failure, we developed exploratory AD and concussion/TBI clinical trial designs.
conclusionsOur findings inform the biomarker indication of progression of pathological targets in neurodegenerations and propose a novel approach to these conditions through neuronal protection against self-induced PPCD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.