ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2013
Fire in the ashes: can failed Alzheimer's disease drugs succeed with second chances?
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Drug repurposing: a systematic review on root causes, barriers and facilitators.BMC health services research · 2022Pooled it
- Enhancing latent cognitive capacity in mild cognitive impairment with gist reasoning training: a pilot study.International journal of geriatric psychiatry · 2017Trial
- Reevaluating Mask Effectiveness: Insights From Evidence-Based Medicine and Clinical Trials.Cureus · 2024Review
- Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine.AAPS PharmSciTech · 2024Article
- Activity Models of Key GPCR Families in the Central Nervous System: A Tool for Many Purposes.Journal of chemical information and modeling · 2023Article
- High-fat diet-associated cognitive decline: Is zinc finger protein 1 (ZPR1) the molecular connection?Current research in physiology · 2021Review
- Does traumatic brain injury hold the key to the Alzheimer's disease puzzle?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Review
- Nicotinic ACh receptors as therapeutic targets in CNS disorders.Trends in pharmacological sciences · 2015Review
- Insulin resistance in Alzheimer's disease.Neurobiology of disease · 2014Review
- Amyloid-β precursor protein synthesis inhibitors for Alzheimer's disease treatment.Annals of neurology · 2014Article
- PPARγ recruitment to active ERK during memory consolidation is required for Alzheimer's disease-related cognitive enhancement.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- A new regulatory road-map for Alzheimer's disease drug development.Current Alzheimer research · 2014Review
- Cognitive enhancing treatment with a PPARγ agonist normalizes dentate granule cell presynaptic function in Tg2576 APP mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- (-)-Phenserine attenuates soman-induced neuropathology.PloS one · 2014Article
- J-147 a Novel Hydrazide Lead Compound to Treat Neurodegeneration: CeeToxJournal of neurology & neurophysiology · 2013Article
- Neurotrophic and neuroprotective actions of (-)- and (+)-phenserine, candidate drugs for Alzheimer's disease.PloS one · 2013Article
- Synthesis of the Alzheimer drug Posiphen into its primary metabolic products (+)-N1-norPosiphen, (+)-N8-norPosiphen and (+)-N1, N8-bisnorPosiphen, their inhibition of amyloid precursor protein, α-Synuclein synthesis, interleukin-1β release, and cholinergic action.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2013Article
- Increasing the success rate for Alzheimer's disease drug discovery and development.Expert opinion on drug discovery · 2012Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
backgroundSince Cognex, more than 200 Alzheimer's disease (AD) drug candidates have failed. Investigations have identified vulnerabilities of these AD drug developments to methodological errors. (-)-Phenserine has been discussed as possibly failing due to flawed methods and practices in development.
methodsWe analyzed documentation of (-)-phenserine's development for vulnerabilities to errors and designed interventions for a redevelopment that could provide fair or unbiased assessments of (-)-phenserine target engagement, target relevance for human diseases, and adequate presumptive evidence of efficacy as a therapeutic for one or more diagnoses to justify registration-required clinical trials.
resultsSimilar to studies of 40 other AD developments, with (-)-phenserine, we found little evidence of preemptive interventions against potentially invalidating errors, grounds to judge progress in development through stages as not scientifically justifiable, and variance excess and placebo group improvements as capable of accounting for outcomes from various studies in the development. We propose to compare a redevelopment resourced to counter these deficiencies with the original development as historical control to evaluate further our hypothesis that errors in development accounted for the (-)-phenserine failure, specifically, and other AD drug failures, potentially.
conclusionsWe find support for our earlier proposal that (-)-phenserine did not fail, but the methods of development did fail, to provide conditions where efficacy could be tested. We propose that redevelopment under conditions aimed to correct methodological deficiencies common in AD drug developments will successfully test efficacy for (-)-phenserine and hopefully lead to a disease-modifying addition to the AD therapeutic armamentarium.
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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.