CT1812, a Small Molecule Sigma-2 Receptor Antagonist for Alzheimer's Disease Treatment: A Systematic Review of Available Clinical Data
Issued Date
2024-01-01
Resource Type
eISSN
18758908
Scopus ID
2-s2.0-85206844595
Pubmed ID
39422939
Journal Title
Journal of Alzheimer's disease : JAD
Volume
101
Issue
s1
Start Page
S115
End Page
S128
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Alzheimer's disease : JAD Vol.101 No.s1 (2024) , S115-S128
Suggested Citation
Thitilertdecha P., Brimson J.M. CT1812, a Small Molecule Sigma-2 Receptor Antagonist for Alzheimer's Disease Treatment: A Systematic Review of Available Clinical Data. Journal of Alzheimer's disease : JAD Vol.101 No.s1 (2024) , S115-S128. S128. doi:10.3233/JAD-230994 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101764
Title
CT1812, a Small Molecule Sigma-2 Receptor Antagonist for Alzheimer's Disease Treatment: A Systematic Review of Available Clinical Data
Author(s)
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Alzheimer's disease (AD) is of growing concern worldwide as the demographic changes to a more aged population. Amyloid-β (Aβ deposition is thought to be a key target for treating AD. However, Aβ antibodies have had mixed results, and there is concern over their safety. Studies have shown that the sigma-2 receptor (σ-2R)/TMEM97 is a binding site for Aβ oligomers. Therefore, targeting the receptor may be beneficial in displacing Aβ oligomers from the brain. CT1812 is a σ-2R/TMEM97 antagonist that is effective in preclinical studies of AD and has been entered into clinical trials. Objective: The objective of this study was to systematically review the safety and efficacy of CT1812 for the treatment of AD. Methods: Between June and August 2023, we searched the primary literature (PubMed, Scopus, Google Scholar, etc.) and clinical trials databases (http://www.clinicaltrails.gov). The extracted data is evaluated within this manuscript. Results: CT1812 is relatively safe, with only mild adverse events reported at doses up to 840 mg. CT1812 can displace Aβ in the clinical studies, in line with the preclinical data. Studies have investigated brain connectivity and function in response to CT1812. However, the cognitive data is still lacking, with only one study including cognitive data as a secondary outcome. Conclusions: CT1812 safely works to displace Aβ however, whether this is enough to prevent/slow the cognitive decline seen in AD remains to be seen. Longer clinical trials are needed to assess the efficacy of CT1812; several trials of this nature are currently ongoing.