Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2021
Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.
Trial report in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02907567 (A Randomized, Double-Blind, Placebo-Controlled, Phase I Study of the Safety & Pharmacokinetics of Two Doses of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 49 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.
A Randomized, Double-Blind, Placebo-Controlled, Phase I Study of the Safety & Pharmacokinetics of Two Doses of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Impact of zervimesine on the neuroinflammatory biomarker GFAP and related proteomic molecular correlates in plasma of participants from a phase 2 clinical trial in Alzheimer's disease.Alzheimer's research & therapy · 2026Trial
- Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB).Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2024Trial
- A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer's disease using an indwelling CSF catheter.Translational neurodegeneration · 2023Trial
- Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Trial
- Crystal Structure of the Sigma‑2 Receptor Complexed with Investigational Drug Zervimesine (CT1812).ACS medicinal chemistry letters · 2026Article
- CT1812 Attenuates Surgery-Induced Cognitive Impairment and Modulates TMEM97- and PGRMC1-Associated Hippocampal Stress Responses in Aged Mice.Neurochemical research · 2026Article
- Structural Assessment of Fibrillated Beta Amyloid to Reveal the Potential Epitopes for Alzheimer's Disease.Cell biochemistry and biophysics · 2026Article
- The mechanisms and strategies for Alzheimer's disease prevention: An update.Acta pharmaceutica Sinica. B · 2026Review
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Advances in the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026Review
- Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.Molecular neurobiology · 2025Article
- Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD).Biomolecules · 2025Review
- Sigma‑2 Receptor/Transmembrane Protein 97 in Pain Modulation: Tracing Historical Roots and Current Research Directions.ACS pharmacology & translational science · 2025Review
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- A Review of the Clinical Progress of CT1812, a Novel Sigma-2 Receptor Antagonist for the Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Recent Advances in Drug Development for Alzheimer's Disease: A Comprehensive Review.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
27 authors at 13 institutions in 5 countries.
Funding
Abstract
introductionAmyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567).
methodsExperiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APP
resultsCT1812 significantly and dose-dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812.
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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.