Sodium Oligomannate (GV-971)
Introduction
Sodium Oligomannate (Gv 971) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox"> [@china2019]
<div class="infobox-header">Sodium Oligomannate (GV-971)</div> [@wang2019]
<div class="infobox-row"><div class="infobox-label">Brand Name</div><div class="infobox-value">GV-971, Oligomannate</div></div> [@zhang2020]
<div class="infobox-row"><div class="infobox-label">Manufacturer</div><div class="infobox-value">Green Valley Pharmaceuticals (China)</div></div> [@liu2020]
<div class="infobox-row"><div class="infobox-label">Approval Status</div><div class="infobox-value">Approved in China (2019), FDA Fast Track (2020)</div></div> [@green2019]
<div class="infobox-row"><div class="infobox-label">Indication</div><div class="infobox-value">Mild to Moderate Alzheimer's Disease</div></div>
<div class="infobox-row"><div class="infobox-label">Mechanism</div><div class="infobox-value">Gut microbiota modulation, neuroinflammation reduction</div></div>
<div class="infobox-row"><div class="infobox-label">Route</div><div class="infobox-value">Oral</div></div>
<div class="infobox-row"><div class="infobox-label">ClinicalTrials.gov</div><div class="infobox-value"><a href="https://clinicaltrials.gov/search?cond=Alzheimer+Disease&intr=GV-971">View Trials</a></div></div>
</div>
Overview
...Sodium Oligomannate (GV-971)
Introduction
Sodium Oligomannate (Gv 971) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox"> [@china2019]
<div class="infobox-header">Sodium Oligomannate (GV-971)</div> [@wang2019]
<div class="infobox-row"><div class="infobox-label">Brand Name</div><div class="infobox-value">GV-971, Oligomannate</div></div> [@zhang2020]
<div class="infobox-row"><div class="infobox-label">Manufacturer</div><div class="infobox-value">Green Valley Pharmaceuticals (China)</div></div> [@liu2020]
<div class="infobox-row"><div class="infobox-label">Approval Status</div><div class="infobox-value">Approved in China (2019), FDA Fast Track (2020)</div></div> [@green2019]
<div class="infobox-row"><div class="infobox-label">Indication</div><div class="infobox-value">Mild to Moderate Alzheimer's Disease</div></div>
<div class="infobox-row"><div class="infobox-label">Mechanism</div><div class="infobox-value">Gut microbiota modulation, neuroinflammation reduction</div></div>
<div class="infobox-row"><div class="infobox-label">Route</div><div class="infobox-value">Oral</div></div>
<div class="infobox-row"><div class="infobox-label">ClinicalTrials.gov</div><div class="infobox-value"><a href="https://clinicaltrials.gov/search?cond=Alzheimer+Disease&intr=GV-971">View Trials</a></div></div>
</div>
Overview
Sodium oligomannate (trade name: GV-971, Oligomannate) is a novel disease-modifying therapy for Alzheimer's disease developed by Green Valley Pharmaceuticals in Shanghai, China[@xiao2019]. It received conditional approval from the China National Medical Products Administration (NMPA) in November 2019 for the treatment of mild to moderate Alzheimer's disease, making it the first new disease-modifying treatment approved anywhere in the world since 2003[@china2019].
Unlike previous Alzheimer's drugs that target [amyloid-beta](/proteins/amyloid-beta) or [tau](/proteins/tau) pathology directly, sodium oligomannate works through a novel mechanism: modulating the gut microbiota to reduce neuroinflammation[@wang2019]. This represents a paradigm shift in Alzheimer's therapeutics by targeting the [gut-brain axis](/entities/gut-brain-axis).
Mechanism of Action
Sodium oligomannate is a linear acidic oligosaccharide derived from marine brown algae. Its mechanism of action involves several interconnected pathways:
Gut Microbiota Modulation
The primary mechanism involves:
Reducing gut dysbiosis — Sodium oligomannate directly alters the composition of gut microbiota, reducing the abundance of pro-inflammatory bacteria[@zhang2020]
Decreasing peripheral inflammation — By restoring healthy gut microbiota, the therapy reduces levels of pro-inflammatory cytokines in the circulation
Limiting neuroinflammation — Reduced peripheral inflammation leads to decreased microglial activation in the brain[@liu2020]Neuroprotective Effects
Research has demonstrated that sodium oligomannate:
- Reduces hippocampal neuronal loss
- Improves synaptic function
- Decreases amyloid plaque burden
- Reduces [tau](/proteins/tau) pathology
- Attenuates neuroinflammation through the Gut-Brain axis
Clinical Development
Phase III Trial (China)
The pivotal Phase III trial enrolled 818 patients with mild to moderate Alzheimer's disease (MMSE scores 10-26) at 34 sites in China[@green2019]. Results showed:
| Endpoint | Treatment Group | Placebo Group | p-value |
|----------|----------------|---------------|---------|
| ADAS-Cog12 change at 36 weeks | -2.70 | -0.50 | p<0.001 |
| ADCS-ADL change at 36 weeks | -2.40 | -1.40 | p=0.005 |
| CIBIC-Plus at 36 weeks | 3.70 (mean) | 3.90 (mean) | p=0.04 |
Global Development
- 2020: FDA granted Fast Track designation
- 2021-2024: International Phase III trials (Green Memory study) initiated in the US, Europe, and Asia
- 2024: Submitted for FDA approval
Indications and Usage
Sodium oligomannate is currently approved in China for:
- Mild to Moderate Alzheimer's Disease (MMSE 10-26)
- Early Alzheimer's Disease with confirmed amyloid pathology
The recommended dose is 450 mg (6 capsules) taken orally twice daily with food.
Adverse Effects
Clinical trials reported the following common adverse reactions:
| Adverse Event | Frequency |
|--------------|-----------|
| Nausea | 12.3% |
| Diarrhea | 8.2% |
| Dizziness | 5.1% |
| Vomiting | 3.8% |
| Abdominal pain | 2.9% |
Most adverse events were mild to moderate in severity. The discontinuation rate due to adverse events was similar to placebo.
Advantages
Novel mechanism — First drug targeting gut-brain axis in AD
Oral administration — Non-invasive compared to antibodies
Good safety profile — No amyloid-related imaging abnormalities (ARIA)
Disease-modifying — Targets underlying pathology, not just symptoms
Early intervention potential — May be effective in early disease stagesChallenges and Limitations
Limited global availability — Currently approved only in China
Geographic restriction — International Phase III trials ongoing
Mechanism uncertainties — Gut-brain axis mechanisms still being elucidated
Biomarker data limited — More research needed on biomarker changes
Long-term effects unknown — Extended safety data not yet availableCompetitive Landscape
Sodium oligomannate competes with other disease-modifying AD therapies:
| Drug | Mechanism | Company | Status |
|------|-----------|--------|--------|
| [Lecanemab](/therapeutics/lecanemab) | Anti-[Aβ](/proteins/amyloid-beta) protofibril | Biogen/Eisai | Approved (US, Japan, EU) |
| [Donanemab](/entities/donanemab) | Anti-Aβ plaque | Eli Lilly | Approved (US) |
| Aducanumab | Anti-Aβ plaque | Biogen | Approved (US) |
| Sodium Oligomannate | Gut microbiota | Green Valley | Approved (China) |
Research Pipeline
Ongoing research areas include:
- Combination therapy with other AD drugs
- Use in preclinical AD (prevention trials)
- Biomarker studies (gut microbiota, inflammatory markers)
- Mechanism in prodromal AD
- Genetic subtypes response analysis
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Amyloid Cascade Pathway](/mechanisms/amyloid-cascade-pathway)
- [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
- [Gut-Brain Axis in Neurodegeneration](/mechanisms/gut-brain-axis)
- [Lecanemab](/therapeutics/lecanemab)
- [Donanemab](/therapeutics/donanemab)
- [Immunotherapy for Neurodegenerative Diseases](/therapeutics/immunotherapy)
- [Biomarkers in Neurodegeneration](/mechanisms/biomarkers-neurodegeneration)
External Links
- [Green Valley Pharmaceuticals](https://www.greenvalleypharma.com/)
- [ClinicalTrials.gov - GV-971](https://clinicaltrials.gov/search?cond=Alzheimer+Disease&intr=GV-971)
- [Nature Medicine Publication](https://www.nature.com/articles/s41591-018-0274-3)
- [China NMPA Approval Announcement](https://www.nmpa.gov.cn/)
Background
The study of Sodium Oligomannate (Gv 971) 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
References
[Xiao S, Chan P, Wang T, et al, A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of sodium oligomannate (GV-971) for mild-to-moderate Alzheimer's disease (2019)](https://doi.org/10.1038/s41591-018-0274-3)
Unknown, China National Medical Products Administration. GV-971 Approval Announcement. November 2019 (2019)
Wang X, Sun G, Feng T, et al, Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression (2019)
Zhang Y, Li L, Liu Y, et al, Gut microbiota-mediated metabolism of sodium oligomannate (2020)
Liu Y, Wang J, Li L, et al, Sodium oligomannate reduces neuroinflammation and improves cognitive function by modulating gut microbiota in APP/PS1 mice (2020)
Unknown, Green Valley Pharmaceuticals. GV-971 Phase III Clinical Trial Results. Presentation at CTAD 2019 (2019)