ArticleAlzheimer's & dementia (New York, N. Y.)
Identification of cerebrospinal fluid pharmacodynamic biomarkers and molecular correlates of brain activity in a Phase 2 clinical trial of the Alzheimer's disease drug candidate CT1812.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04735536 (A Pilot Electroencephalography), which is not on this map. Cited by 1 paper.
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 Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects With Mild to Moderate Alzheimer's Disease
Who cites it
1 citing paper in PubMed.
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCT1812 (zervimesine) is an orally dosed modulator of the sigma-2 receptor (S2R) currently in clinical development for the treatment of Alzheimer's disease (AD). CT1812 has been shown in preclinical and early clinical trials to selectively prevent and displace binding of amyloid beta oligomers from their synaptic receptors and has improved cognitive function in animal models of AD.
methodsSEQUEL (NCT04735536) is a completed Phase 2, randomized, placebo-controlled 4-week crossover trial in adults with mild-to-moderate AD that investigated the effect of CT1812 on safety, synaptic function using quantitative electroencephalography (qEEG), and biomarkers. CT1812 improved established qEEG markers of spontaneous brain activity, suggesting improved neuronal and synaptic function. In the present study, cerebrospinal fluid (CSF)-based tandem mass tag mass spectrometry (TMT-MS) was performed on participant samples to investigate proteomic effects and identify potential biomarkers of CT1812.
resultsBiomarkers found through proteomics analyses to be significantly differentially abundant in CT1812- versus placebo-treated participants supported pathway engagement and proof of mechanism for CT1812. Impacted proteins support a role for CT1812 at synapses, in vesicle trafficking, and in lipoprotein biology. Biomarkers correlated with the previously reported improvements in qEEG-based functional connectivity (inferred through alpha band Amplitude Envelope Correlations) with CT1812 treatment were also identified and may be potential early surrogate biomarkers of efficacy for CT1812. The processes and functions supported by biomarkers were congruent with those previously revealed in CSF proteomics analyses from phase 1 and 2 AD clinical trials with CT1812. DISCUSSION: After 1 month of treatment, the identification of biomarkers supporting pathway engagement, the replication of biomarker findings from prior trials, and the discovery of molecular correlates of improved functional connectivity with CT1812 treatment bolster support for and expound upon the mechanism of action for CT1812 in displacing Aβ oligomers at neuronal synapses, as well as underscores the CT1812 relevance to AD. Highlights: Exploratory proteomics identified candidate CSF biomarkers of CT1812 in SEQUEL.Molecular correlates of functional brain connectivity (qEEG) were identified.Proteins impacted by 1 month CT1812 treatment support target engagement.Pharmacodynamic changes found in synapse, immune, vesicle, and lipoprotein biologies.SEQUEL proteomics findings replicated previous trial findings with CT1812.
Indexed as
Identifiers
What Socratic 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 Socratic graph.