CuATSM (Copper(II)-diacetyl-bis(N4-methylthiosemicarbazone))

CuATSM (CuII(atsm))

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">CuATSM (Copper(II)-diacetyl-bis(N4-methylthiosemicarbazone))</th>
</tr>
<tr>
<td class="label">Category</td>
<td>Copper Delivery / Mitochondrial Function</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Mitochondrial dysfunction, Oxidative stress</td>
</tr>
<tr>
<td class="label">Route</td>
<td>Oral</td>
</tr>
<tr>
<td class="label">Company</td>
<td>OpTerra Therapeutics</td>
</tr>
<tr>
<td class="label">Clinical Phase</td>
<td>Phase 2</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>CuATSM</td>
</tr>
<tr>
<td class="label">Mechanism</td>
<td>Mito. function</td>
</tr>
<tr>
<td class="label">Target</td>
<td>General mito.</td>
</tr>
<tr>
<td class="label">Route</td>
<td>Oral</td>
</tr>
<tr>
<td class="label">ALS mutation</td>
<td>All types</td>
</tr>
<tr>
<td class="label">Biomarker</td>
<td>Expected Change</td>
</tr>
<tr>
<td class="label">Mito. Complex IV activity</td>
<td>Increase</td>
</tr>
<tr>
<td class="label">8-OHdG (urine)</td>
<td>Decrease</td>
</tr>
<tr>
<td class="label">[NfL](/proteins/nfl-protein)</td>
<td>Decrease/slow rise</td>
</tr>
<tr>
<td class="label">CSF copper</td>
<td>Increase</td>
</tr>
</table>

Introduction

...

CuATSM (CuII(atsm))

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">CuATSM (Copper(II)-diacetyl-bis(N4-methylthiosemicarbazone))</th>
</tr>
<tr>
<td class="label">Category</td>
<td>Copper Delivery / Mitochondrial Function</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Mitochondrial dysfunction, Oxidative stress</td>
</tr>
<tr>
<td class="label">Route</td>
<td>Oral</td>
</tr>
<tr>
<td class="label">Company</td>
<td>OpTerra Therapeutics</td>
</tr>
<tr>
<td class="label">Clinical Phase</td>
<td>Phase 2</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>CuATSM</td>
</tr>
<tr>
<td class="label">Mechanism</td>
<td>Mito. function</td>
</tr>
<tr>
<td class="label">Target</td>
<td>General mito.</td>
</tr>
<tr>
<td class="label">Route</td>
<td>Oral</td>
</tr>
<tr>
<td class="label">ALS mutation</td>
<td>All types</td>
</tr>
<tr>
<td class="label">Biomarker</td>
<td>Expected Change</td>
</tr>
<tr>
<td class="label">Mito. Complex IV activity</td>
<td>Increase</td>
</tr>
<tr>
<td class="label">8-OHdG (urine)</td>
<td>Decrease</td>
</tr>
<tr>
<td class="label">[NfL](/proteins/nfl-protein)</td>
<td>Decrease/slow rise</td>
</tr>
<tr>
<td class="label">CSF copper</td>
<td>Increase</td>
</tr>
</table>

Introduction

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](/entities/neurons) and shows promise for treating amyotrophic lateral sclerosis, Parkinson's disease, and other neurodegenerative conditions. [@copper2022]

Overview

Mechanism of Action

CuATSM is a mitochondria-targeting copper chelator that works through multiple pathways:

1. Mitochondrial Copper Delivery

• Crosses the [blood-brain barrier](/entities/blood-brain-barrier) efficiently
• Selectively accumulates in mitochondria
• Delivers copper to mitochondrial enzymes
• Restores cytochrome c oxidase (Complex IV) activity

2. Antioxidant Effects

• Scavenges reactive oxygen species (ROS)
• Reduces lipid peroxidation
• Activates Nrf2 antioxidant response
• Protects against oxidative damage

3. Anti-Inflammatory Activity

• Modulates microglial activation
• Reduces pro-inflammatory cytokines
• May inhibit [NLRP3](/entities/nlrp3-inflammasome) inflammasome

4. Neuroprotection

• Promotes mitochondrial biogenesis
• Enhances cellular energy production
• Protects against excitotoxicity
• Supports axonal integrity

Clinical Development

Preclinical Studies

• 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

Phase 1 Study

• Single and multiple ascending dose in healthy volunteers
• Demonstrated safety and tolerability
• Achieved target brain concentrations
• Good oral bioavailability

Phase 2 Study (CUDOS-ALS)

• 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

Phase 2 Study (CUDOS-PD)

• Trial in patients with early Parkinson's disease
• Primary endpoint: Motor symptoms (MDS-UPDRS)
• Secondary endpoints: Dopaminergic imaging, biomarkers
• Evaluating disease-modifying potential

Therapeutic Potential

Amyotrophic Lateral Sclerosis

• 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

Parkinson's Disease

• Protects dopaminergic neurons
• May improve mitochondrial Complex I activity
• Addresses oxidative stress in PD pathogenesis
• Being studied as disease-modifying agent

Huntington's Disease

• Mitochondrial dysfunction is central to HD
• May protect striatal neurons
• Could improve motor and cognitive symptoms

Multiple System Atrophy

• Addresses mitochondrial deficits in oligodendrocytes
• May slow disease progression

Comparison: CuATSM vs. Other Approaches

Biomarkers Under Study

Research Directions

• Biomarker development for patient selection
• Earlier intervention trials
• Combination with antisense oligonucleotides
• Preventive trials in genetic forms

Background

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.

Allen Brain Atlas Resources

• [Allen Brain Atlas - Gene Expression](https://human.brain-map.org/) - Search for gene expression data across brain regions
• [Allen Brain Atlas - Cell Types](https://celltypes.brain-map.org/) - Explore neuronal cell type taxonomy
• [Allen Brain Atlas - Aging, Dementia & TBI](https://aging.brain-map.org/) - Data on aging and traumatic brain injury

See Also

• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction)
• [Oxidative Stress Pathway](/mechanisms/oxidative-stress)
• [ALS Treatments](/content/treatments)
• [Parkinson's Disease Treatments](/content/treatments)
• [Copper Metabolism](/mechanisms/metal-homeostasis)

External Links

• [OpTerra Therapeutics](https://www.opterrathera.com)
• [ALS Association](https://www.alsassociation.org)
• [Michael J. Fox Foundation](https://www.michaeljfox.org)
• [ClinicalTrials.gov: CuATSM](https://clinicaltrials.gov)

References

Unknown, [^1] CuATSM: A Mitochondria-Targeting Compound for Neurodegeneration (2023)

Unknown, [^2] Copper Delivery to Mitochondria by CuATSM (2022)

Unknown, [^3] CuATSM in ALS Mouse Model (2021)

Unknown, [^4] Phase 1 Study of CuATSM in Healthy Volunteers (2022)

Unknown, [^5] CUDOS-ALS: Phase 2 Study Results (2024)

Unknown, [^6] CuATSM in Parkinson's Disease Models (2023)

Unknown, [^7] Mitochondrial Dysfunction in Neurodegeneration (2022)

Unknown, [^8] Copper in Brain Health and Disease (2024)

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Bacterial Enzyme-Mediated Dopamine Precursor Synthesis](/hypothesis/h-7bb47d7a) — <span style="color:#ffd54f;font-weight:600">0.44</span> · Target: TH, AADC
• [Microbial Inflammasome Priming Prevention](/hypothesis/h-e7e1f943) — <span style="color:#81c784;font-weight:600">0.76</span> · Target: NLRP3, CASP1, IL1B, PYCARD

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