Axsome Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing novel therapies for central nervous system (CNS) disorders. Founded in 2012 and headquartered in New York, Axsome focuses on addressing unmet needs in neuropsychiatry, particularly in Alzheimer's disease, depression, and sleep disorders[1].
| Drug | Mechanism | Stage | Status |
|---|---|---|---|
| AXS-060 | Sigma-1 receptor agonist / M1 muscarinic modulator | Phase 2/3 | Recruiting |
| AXS-05 | NMDA receptor antagonist / sigma-1 agonist | Phase 2 | Completed |
AXS-060 (formerly known as ACD-680) is a novel, first-in-class, orally administered sigma-1 receptor agonist being developed for the treatment of agitation and other neuropsychiatric symptoms in Alzheimer's disease. Sigma-1 receptors are highly expressed in brain regions involved in cognition and emotion, including the hippocampus and prefrontal cortex[2].
The sigma-1 receptor is a chaperone protein located at the endoplasmic reticulum-mitochondria interface that plays a critical role in:
Preclinical studies have demonstrated that sigma-1 receptor activation reduces neuroinflammation, protects against excitotoxicity, and improves cognitive function in animal models of Alzheimer's disease[3].
| Drug | Indication | Mechanism | Stage |
|---|---|---|---|
| AXS-05 | Major depressive disorder | NMDA antagonist + sigma-1 agonist | Phase 3 |
| AXS-07 | Migraine | CGRP antagonist / 5-HT1F agonist | Phase 3 |
| AXS-12 | Narcolepsy | Norepinephrine reuptake inhibitor | Phase 2 |
The sigma-1 receptor is an unusual intracellular receptor that acts as a molecular chaperone. Unlike traditional neurotransmitter receptors, sigma-1 receptors modulate multiple signaling pathways:
In Alzheimer's disease, sigma-1 receptor function may be impaired, leading to:
AXS-060 aims to restore sigma-1 receptor function, potentially addressing multiple aspects of Alzheimer's disease pathology[4].
Axsome's approach with sigma-1 receptor agonism represents a novel mechanism in Alzheimer's disease, differentiating it from:
Alzheimer's Disease Treatment
Neuroinflammation in AD
Sigma-1 Receptor
Behavioral Symptoms of Dementia