Cognition Therapeutics Publishes Results Of Proteomics Analysis From Phase 2 'SEQUEL' COG0202 Study Of Zervimesine In Adults With Mild-To-Moderate Alzheimer's Disease
Benzinga Newsdesk 1 year ago
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Cognition Therapeutics, Inc., (the "Company" or "Cognition") (NASDAQ:CGTX), a clinical-stage company developing drugs that treat neurodegenerative disorders, published results of a proteomics analysis from the Phase 2
Cognition Therapeutics, Inc., (the "Company" or "Cognition") (NASDAQ:CGTX), a clinical-stage company developing drugs that treat neurodegenerative disorders, published results of a proteomics analysis from the Phase 2 ‘SEQUEL' COG0202 Study of zervimesine (CT1812) in adults with mild-to-moderate Alzheimer's disease. The manuscript, titled 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, was published in the peer-reviewed journal Alzheimer's & Dementia: Translational Research & Clinical Interventions. SEQUEL was a single-site study that investigated the effect of zervimesine on synaptic function using quantitative electroencephalography (qEEG), a noninvasive technique to measure electrical activity of the brain.
In the SEQUEL study (NCT04735536), zervimesine treatment resulted in consistent trends of improvement across all prespecified EEG parameters, including the prominence of certain EEG frequencies associated with Alzheimer's disease. Slower frequencies termed "theta" waves were reduced after 29 days of zervimesine treatment compared to placebo. This suggests zervimesine may normalize the function of neurons and synapses.
Additionally, zervimesine treatment was associated with an improvement in global alpha AEC-c, a measure of functional connectivity, suggesting zervimesine may be facilitating communication between brain regions. Analysis was performed to identify proteins associated with zervimesine's normalizing effect on AEC-c. Proteins that were significantly altered with zervimesine treatment compared to placebo were associated with vesicle formation, exocytosis and endosomal trafficking. These key cellular functions allow neurons to recycle and eject cellular debris, and transport cargo needed for cellular function.
In vitro studies were conducted using neurons derived from a human cell line. Neurons cultured in this way possess many of the functions of cells in the brain. They form long branches that make connections with neighboring cells, move cargo through cells, and recycle cell waste. They may also be damaged by the same toxic elements that drive neurodegenerative disease, such as oxidative stress, which contributes to disease progression. In this way, these cell cultures are useful models of disease states.
4-Hydroxynonenal (4-HNE) is a naturally occurring molecule known to induce oxidative stress. 4-HNE is found in high levels in the brains of people with neurodegenerative diseases. When added to a culture of neurons in this study, cells began to die as soon as four hours after exposure to 4-HNE. By 24 hours, more than 50% of the cells had died. This was evident not only by the visual appearance of the culture, but also by an increase in levels of a structural protein called neurofilament light (NfL) that was released from dying neurons into the culture medium. However, when zervimesine was added with the 4-HNE to the cultures, cell viability was preserved, and cellular levels of NfL were also maintained, attesting to the structural integrity of the neurons.
Further study showed zervimesine was able to preserve cell integrity and function in the face of a toxic compound such as 4-HNE by interrupting 4-HNE's ability to induce cell death.