ML-007C-MA Phase 2 (NCT06887192): Novel M₁/M₄ Agonist for Alzheimer's Disease Psychosis
Overview
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ML-007C-MA is a novel M1/M₄ muscarinic acetylcholine receptor agonist being developed by MapLight Therapeutics for the treatment of hallucinations and delusions associated with Alzheimer's Disease Psychosis (ADP). This Phase 2 trial (NCT06887192) is currently recruiting participants to evaluate the efficacy and safety of ML-007C-MA in AD patients with psychotic symptoms["@clinicaltrialsgov"][@maplightpipeline].
...ML-007C-MA Phase 2 (NCT06887192): Novel M₁/M₄ Agonist for Alzheimer's Disease Psychosis
Overview
Mermaid diagram (expand to render)
ML-007C-MA is a novel M1/M₄ muscarinic acetylcholine receptor agonist being developed by MapLight Therapeutics for the treatment of hallucinations and delusions associated with Alzheimer's Disease Psychosis (ADP). This Phase 2 trial (NCT06887192) is currently recruiting participants to evaluate the efficacy and safety of ML-007C-MA in AD patients with psychotic symptoms["@clinicaltrialsgov"][@maplightpipeline].
Alzheimer's disease psychosis represents a significant unmet need, affecting approximately 30-50% of Alzheimer's disease patients during the disease course. It manifests as visual or auditory hallucinations and delusional thinking, dramatically impacting patient safety, quality of life, and caregiver burden["@ipap2020"].
| Attribute | Details |
|-----------|---------|
| NCT Number | NCT06887192 |
| Sponsor | MapLight Therapeutics |
| Drug | ML-007C-MA |
| Phase | Phase 2 |
| Indication | Alzheimer's Disease Psychosis |
| Status | Recruiting |
| Participants | 300 |
| Study Start | August 2025 |
| Estimated Completion | December 2027 |
Mechanism of Action
Dual Muscarinic Agonism
ML-007C-MA is a novel M₁/M₄ muscarinic acetylcholine receptor agonist. This mechanism differs from current antipsychotic treatments, which primarily target dopamine and serotonin receptors. By selectively activating central M₁ and M₄ receptors, ML-007C-MA aims to address both the cognitive and psychotic symptoms of Alzheimer's disease[@maplightpipeline].
Receptor Pharmacology
| Receptor | Location | Effect | Therapeutic Implication |
|----------|----------|--------|------------------------|
| M1 | Central | Cognitive enhancement | Memory and learning improvement |
| M4 | Central | Anti-psychotic effect | Reduction of hallucinations and delusions |
| M2/M3 | Peripheral | Autonomic effects | Managed through drug design |
Rationale for Muscarinic Agonism in ADP
The cholinergic system is severely compromised in Alzheimer's disease:
- Basal forebrain cholinergic neurons degenerate early in AD
- Cholinergic innervation of cortex and hippocampus diminishes
- Loss correlates with both cognitive decline and behavioral symptoms
- Muscarinic receptor density is preserved in AD brains, making them viable targets
By activating M1/M4 receptors, ML-007C-MA aims to:
Improve cognitive function through M1 receptor signaling
Reduce psychotic symptoms through M4 receptor signaling
Provide a non-dopaminergic approach avoiding antipsychotic side effectsClinical Development
Study Design
The ML-007C-MA-221 study is a Phase 2, randomized, double-blind, placebo-controlled trial:
- Allocation: Randomized (1:1)
- Intervention Model: Parallel assignment
- Masking: Quadruple (participant, care provider, investigator, outcomes assessor)
- Treatment Duration: 7 weeks
Dosing
ML-007C-MA is administered as:
- 105/1.5 mg BID (twice daily), or
- 210/3 mg BID
Eligibility Criteria
Key Inclusion Criteria:
Age 55-90 years
Possible or Probable AD (NIA-AA criteria)
Psychotic symptoms meeting IPA criteria for ≥2 months
NPI-C H+D score ≥6
CGI-S hallucinations and delusions domain score ≥4
MMSE score of 6-26
Has a designated care partnerKey Exclusion Criteria:
Psychotic symptoms primarily due to other causes (substance, medical, neurological)
CNS disorder other than AD as primary cause of dementia
Moderate-severe major depressive episode within 3 months
Elevated suicidal risk
Prior participation in ML-007 or ML-007C-MA studiesEndpoints
Primary Endpoint
- Change from Baseline to End of Treatment in NPI-C Hallucinations and Delusions (H+D) score
- Scale: 7 items for hallucinations (max 21) + 8 items for delusions (max 24) = 45 total
- Higher scores indicate worse outcomes
Secondary Endpoints
CGI-S hallucinations and delusions domain-specific score change
NPI-C Agitation and Aggression (A+A) score change (in participants with baseline CGI-S agitation/aggression ≥4)MapLight Therapeutics
MapLight Therapeutics is a pharmaceutical company focused on developing novel therapeutics targeting symptoms of neurological and psychiatric disorders. Their pipeline includes programs for:
- Autism Spectrum Disorder
- [Parkinson's Disease](/diseases/parkinsons-disease)
- Schizophrenia
- Alzheimer's Disease Psychosis
The company announced Phase 2 trial initiation for ML-007C-MA in September 2025[@maplightpipeline].
Comparison to Other AD Psychosis Treatments
| Treatment | Mechanism | Limitations |
|-----------|-----------|-------------|
| Pimavanserin (Nuplazid) | 5-HT2A inverse agonist | Limited to Parkinson's disease psychosis |
| Risperidone | D2 antagonist | Extrapyramidal symptoms, stroke risk |
| Quetiapine | Multi-receptor | Sedation, metabolic effects |
| ML-007C-MA | M1/M4 agonist | Novel mechanism, Phase 2 |
Safety and Tolerability
As a muscarinic agonist, ML-007C-MA may cause cholinergic adverse events:
- Dry mouth
- Constipation
- Urinary retention
- Nausea
- Dizziness
The novel M₁/M₄ selective profile aims to maximize central therapeutic effects while minimizing peripheral side effects.
Locations
Recruiting sites include multiple locations in the United States and Canada:
- United States: Arizona (Phoenix, Scottsdale, Tucson), California (Anaheim, Orange, San Diego), Florida (Boca Raton, Deerfield Beach, Doral, Homestead, Miami, Miami Gardens, Naples, Orlando, West Palm Beach), Nevada (Las Vegas), New Jersey, Ohio
- Canada: Ontario (Brampton, London, Toronto), Quebec (Lévis)
Cross-Links to NeuroWiki
- [Alzheimer's Disease](/diseases/alzheimers-disease) — Target indication
- [Alzheimer's Disease Psychosis](/diseases/alzheimers-disease-psychosis) — Related condition
- [Cholinergic System](/mechanisms/cholinergic-system) — Mechanism basis
- [Muscarinic Receptors](/entities/muscarinic-receptors) — Drug target
- [MapLight Therapeutics](/companies/maplight-therapeutics) — Sponsor
References
Unknown, ClinicalTrials.gov. NCT06887192: ML-007C-MA for Alzheimer's Disease Psychosis (n.d.)
Unknown, MapLight Therapeutics Pipeline - ML-007C-MA (n.d.)
[Unknown, Muscarinic acetylcholine receptors for psychotic disorders. Pharmacol Ther. 2022 (2022)](https://pubmed.ncbi.nlm.nih.gov/35248236/)
[Unknown, International Psychogeriatric Association criteria for psychosis in Alzheimer's disease. Cummings 2020 (2020)](https://pubmed.ncbi.nlm.nih.gov/32050165/)