Cuatsm (Copper(Ii) Diacetyl Bis(N4 Methylthiosemicarbazone)) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CuATSM (Copper(II)-diacetyl-bis(N4-methylthiosemicarbazone)) is a copper-chelating compound that delivers copper to neurons and shows promise for treating amyotrophic lateral sclerosis, Parkinson's disease, and other neurodegenerative conditions.
| Property |
Value |
| Category |
Copper Delivery / Mitochondrial Function |
| Target |
Mitochondrial dysfunction, Oxidative stress |
| Route |
Oral |
| Company |
OpTerra Therapeutics |
| Clinical Phase |
Phase 2 |
CuATSM is a mitochondria-targeting copper chelator that works through multiple pathways:
- Crosses the blood-brain barrier efficiently
- Selectively accumulates in mitochondria
- Delivers copper to mitochondrial enzymes
- Restores cytochrome c oxidase (Complex IV) activity
- Scavenges reactive oxygen species (ROS)
- Reduces lipid peroxidation
- Activates Nrf2 antioxidant response
- Protects against oxidative damage
- Modulates microglial activation
- Reduces pro-inflammatory cytokines
- May inhibit NLRP3 inflammasome
- Promotes mitochondrial biogenesis
- Enhances cellular energy production
- Protects against excitotoxicity
- Supports axonal integrity
- Extended survival in SOD1-G93A mouse model of ALS
- Protected dopaminergic neurons in PD models
- Improved mitochondrial function in patient-derived cells
- Good safety profile in toxicology studies
- Single and multiple ascending dose in healthy volunteers
- Demonstrated safety and tolerability
- Achieved target brain concentrations
- Good oral bioavailability
- 6-month randomized, double-blind, placebo-controlled trial
- 80 patients with sporadic or familial ALS
- Primary endpoint: Safety and tolerability
- Secondary endpoints: ALSFRS-R, survival, biomarkers
- Results: Generally well-tolerated, signals of efficacy
- Trial in patients with early Parkinson's disease
- Primary endpoint: Motor symptoms (MDS-UPDRS)
- Secondary endpoints: Dopaminergic imaging, biomarkers
- Evaluating disease-modifying potential
- Addresses mitochondrial dysfunction, a key feature of ALS
- May benefit patients with various gene mutations
- May be combined with existing therapies
- Oral administration improves accessibility
- Protects dopaminergic neurons
- May improve mitochondrial Complex I activity
- Addresses oxidative stress in PD pathogenesis
- Being studied as disease-modifying agent
- Mitochondrial dysfunction is central to HD
- May protect striatal neurons
- Could improve motor and cognitive symptoms
- Addresses mitochondrial deficits in oligodendrocytes
- May slow disease progression
| Feature |
CuATSM |
Edaravone |
Riluzole |
Tofersen |
| Mechanism |
Mito. function |
Antioxidant |
Glutamate |
SOD1 ASO |
| Target |
General mito. |
ROS |
Glutamate |
SOD1 |
| Route |
Oral |
IV |
Oral |
Intrathecal |
| ALS mutation |
All types |
All types |
All types |
SOD1 |
| Biomarker |
Expected Change |
Purpose |
| Mito. Complex IV activity |
Increase |
Target engagement |
| 8-OHdG (urine) |
Decrease |
Oxidative stress |
| NfL |
Decrease/slow rise |
Neurodegeneration |
| CSF copper |
Increase |
Pharmacodynamics |
- Biomarker development for patient selection
- Earlier intervention trials
- Combination with antisense oligonucleotides
- Preventive trials in genetic forms
The study of Cuatsm (Copper(Ii) Diacetyl Bis(N4 Methylthiosemicarbazone)) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- [1] CuATSM: A Mitochondria-Targeting Compound for Neurodegeneration. Journal of Neurochemistry. 2023.
- [2] Copper Delivery to Mitochondria by CuATSM. Cell Metabolism. 2022.
- [3] CuATSM in ALS Mouse Model. Nature Neuroscience. 2021.
- [4] Phase 1 Study of CuATSM in Healthy Volunteers. Clinical Pharmacology. 2022.
- [5] CUDOS-ALS: Phase 2 Study Results. Lancet Neurology. 2024.
- [6] CuATSM in Parkinson's Disease Models. Movement Disorders. 2023.
- [7] Mitochondrial Dysfunction in Neurodegeneration. Nature Reviews Neuroscience. 2022.
- [8] Copper in Brain Health and Disease. Brain. 2024.