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AAIC 2022 | Phase II study of S2R modulation in patients with dementia with Lewy bodies

CT1812 is a small molecule sigma-2 receptor (S2R) modulator in development for Alzheimer’s disease (AD). Preclinical data from a cortical neuronal culture system and AD animal models have shown that CT1812 is able to displace amyloid-beta (Aβ) oligomers from synapses and prevent further receptor binding, thereby restoring damaged cellular processes such as autophagy and protein trafficking. Based on this mechanism of action, the team at Cognition Therapeutics wanted to see if S2R modulation could also block toxicity from alpha-synuclein (α-syn) oligomers. Preclinical testing demonstrated that CT1812 was able to block α-syn oligomers from binding to neuronal synapses, restore dysfunctional autophagy, and resolve protein trafficking deficits. CT1812 is therefore being investigated in the Phase II SHIMMER study (NCT05225415) in adults with dementia with Lewy bodies (DLB). This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.