Thank You for YOUR EMAIL

Thank you for your interest in Cognition Therapeutics

Cognition Therapeutics is currently enrolling participants in Phase 2 clinical trials both in Alzheimer’s Disease and dementia with Lewy bodies. Both studies utilize Cognition’s proprietary lead product candidate, CT1812, an orally delivered, small molecule designed to penetrate the blood-brain barrier and bind selectively to the sigma-2 (σ-2) receptor complex, a key regulator of cellular damage and stress response. More information on these studies may be found on www.clinicaltrials.gov.

Alzheimer’s Disease

Alzheimer’s disease is caused by the age-related buildup of proteins including beta amyloid (Aβ). Under normal conditions, the cell removes these proteins from the brain before they are allowed to accumulate and aggregate into more toxic forms. However, in Alzheimer’s disease, the cellular damage response is disrupted, allowing the formation of toxic Aβ oligomers. These oligomeric forms of the Aβ protein bind to synapses where they cause a cascade of damage and eventual loss of neurons.

Dementia with Lewy Bodies

Dementia with Lewy bodies (DLB) involves a neurodegenerative, progressive decline in motor and cognitive dysfunction. DLB is associated with the accumulation of the protein α-synuclein, which aggregates into fibrils, the major constituent of the Lewy bodies that occur inside brain neurons.

Only a few symptomatic treatments are approved today for these patients.

Cognition Presentations and Publications

AD/PD™ 2022

Analyses from clinical studies of CT1812 in patients with Alzheimer’s disease were presented at AD/PD™ 2022. 

Publications

Cognition Therapeutics has several publications on the sigma-2 receptor, its role in neurological disorders such as Alzheimer’s disease and results of earlier studies. 

click to open and download

click to open and download

CT1812 for the Treatment of Alzheimer's Disease

Rishton GM, Look GC, Ni Z-J, et al. Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer’s Disease. ACS Med Chem Lett. 2021 Aug 9;12(9):1389-1395.

BioMarker Studies and Findings

Izzo NJ, Yuede CM, LaBarbera KM, et al. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer’s disease modification. Alzheimer’s Dement. 2021 Aug; 17(8):1365-1382

Colom-Cadena M, Spires-Jones T, Zetterberg H, et al. The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease. Alz Res Therapy 12, 21 (2020)

CT1812 for the Treatment of Synucleinopathies

Limegrover CS, LeVine H III, Izzo NJ, et al. Alzheimer’s Protection Effect of A673T Mutation May Be Driven by Lower Aβ Oligomer Binding Affinity. J Neurochem. 2020; 00: 1– 15. doi:10.1111/jnc.15212

Sigma-2 Receptor Biology

Colom-Cadena M, Tulloch J, Jackson RJ, et al. TMEM97 increases in synapses and is a potential synaptic Aβ binding partner in human Alzheimer’s disease. bioRxiv 2021.02.01.428238; doi.org/10.1101/2021.02.01.428238

Izzo NJ, Colom-Cadena M, Riad AA, et al. Proceedings from the Fourth International Symposium on σ-2 Receptors: Role in Health and Disease. 7(6) ENEURO .0317-20.2020 1–7

Supportive Industry Publications

Sigma-2 Receptor Complex Biology and Role in Disease

Alon A, Schmidt HR, et al. Identification of the gene that codes for the σ2 receptor. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7160-7165

Synaptotoxicity of Aβ Oligomers

Cline EN, Bicca MA, et al. The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade. J Alzheimers Dis. 2018; 64(s1):S567-S610

Selkoe DJ, Hardy J. The Amyloid Hypothesis of Alzheimer’s Disease at 25 Years. EMBO Molecular Medicine. 2016 Jun; 8(6):595-608

BioMarkers of Disease and Target Engagement

Schindler SE, Li Y, et al; Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2019 May;15(5):655-665

Dhiman K, Blennow K, et al. Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer’s disease pathogenesis. Cell Mol Life Sci. 2019 May;76(10):1833-1863

Novel Approach

The sigma-2 (σ-2) receptor is expressed by multiple cell types, including neuronal synapses, and acts as a key regulator of cellular damage commonly associated with certain age-related degenerative diseases of the CNS and retina. The σ-2 complex is comprised of transmembrane protein 97 (TMEM97), a four-domain transmembrane protein that forms a complex with progesterone receptor membrane component 1 (PGRMC1).

The σ-2 complex is expressed in the CNS, the retina, as well as peripheral organs, including the pancreas, liver and kidney. Within the brain, the σ-2 complex is found in several areas, including the cerebellum, cortex, hippocampus and substantia nigra, and is enriched in neurons as compared to glial cells in the adult brain. In the retina, the σ-2 complex is expressed in several cell types including the RPE cells, photoreceptors and retinal ganglion cells.

We believe that targeting the σ-2 complex represents a mechanism that is functionally distinct from other current approaches in clinical development for the treatment of degenerative diseases.

Additional Questions? Email our Communications Team:

Scroll to Top

Thank you

Someone from the Cognition Therapeutics team
will be in touch with you soon.