Trial reportJournal of neurology, neurosurgery, and psychiatry2012
Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans.
Trial report in Journal of neurology, neurosurgery, and psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- A Systematic Review on Disease-Modifying Therapies in Parkinsonian Disorders.Clinical pharmacology and therapeutics · 2026Pooled it
- A phase 1, safety, tolerability, and pharmacokinetics study of bisnorcymserine, a highly selective inhibitor of butyrylcholinesterase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Trial
- A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease.Alzheimer's research & therapy · 2024Trial
- Analysis of the Efficacy of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease, Literature Review.International journal of molecular sciences · 2026Review
- Structural Assessment of Fibrillated Beta Amyloid to Reveal the Potential Epitopes for Alzheimer's Disease.Cell biochemistry and biophysics · 2026Article
- Small-Molecule Targeting of the Iron-Responsive Element in the APP mRNA 5'-UTR to Control Amyloid Translation in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.Biomolecules · 2025Article
- Bioavailability as Proof to Authorize the Clinical Testing of Neurodegenerative Drugs-Protocols and Advice for the FDA to Meet the ALS Act Vision.International journal of molecular sciences · 2024Review
- APP dyshomeostasis in the pathogenesis of Alzheimer's disease: implications for current drug targets.Alzheimer's research & therapy · 2024Review
- Comparative Analysis of Posiphen Pharmacokinetics across Different Species-Similar Absorption and Metabolism in Mouse, Rat, Dog and Human.Biomolecules · 2024Article
- A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with Early Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2024Article
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
- The role of basket trials in drug development for neurodegenerative disorders.Alzheimer's research & therapy · 2022Review
- Article
- Intertwined Relation between the Endoplasmic Reticulum and Mitochondria in Ischemic Stroke.Oxidative medicine and cellular longevity · 2022Review
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- New Understanding on the Pathophysiology and Treatment of Constipation in Parkinson's Disease.Frontiers in aging neuroscience · 2022Review
- Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression.Pharmaceutics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
aimA first in human study to evaluate tolerability and pharmacokinetics followed by an early proof of mechanism (POM) study to determine whether the small orally, available molecule, Posiphen tartrate (Posiphen), lowers secreted (s) amyloid-β precursor protein (APP) α and -β, amyloid-β peptide (Aβ), tau (τ) and inflammatory markers in CSF of patients with mild cognitive impairment (MCI). STUDY
designPosiphen single and multiple ascending dose phase 1 randomised, double blind, placebo-controlled safety, tolerance, pharmacokinetic studies were undertaken in a total of 120 healthy volunteers to define a dose that was then used in a small non-randomised study of five MCI subjects, used as their own controls, to define target engagement.
main outcome measuresPharmacodynamic: sAPPα, sAPPβ, Aβ(42), τ (total (t) and phosphorylated (p)) and inflammatory marker levels were time-dependently measured over 12 h and compared prior to and following 10 days of oral Posiphen treatment in four MCI subjects who completed the study. Pharmacokinetic: plasma and CSF drug and primary metabolite concentrations with estimated brain levels extrapolated from steady-state drug administration in rats.
resultsPosiphen proved well tolerated and significantly lowered CSF levels of sAPPα, sAPPβ, t-τ, p-τ and specific inflammatory markers, and demonstrated a trend to lower CSF Aβ(42).
conclusionsThese results confirm preclinical POM studies, demonstrate that pharmacologically relevant drug/metabolite levels reach brain and support the continued clinical optimisation and evaluation of Posiphen for MCI and Alzheimer's disease.
Indexed as
Identifiers
What OpenQuestion holds
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.