Sodium oligomannate, also known as GV-971, is a therapeutic drug developed for individuals with mild to moderate Alzheimer’s disease. Originating from a type of brown seaweed, it is a sugar-based compound. The development of this drug represents a different approach to treatment, with the primary goal of improving cognitive function. The drug was developed over a 22-year period through a collaboration involving the Ocean University of China, the Shanghai Institute of Materia Medica, and Shanghai Green Valley Pharmaceutical Co. Ltd.
Proposed Mechanism of Action
The proposed mechanism for sodium oligomannate centers on the relationship between the gut and the brain, often called the gut-brain axis. The drug is not absorbed into the bloodstream but acts within the gastrointestinal tract. There, it is thought to remodel the gut microbiome, the community of microorganisms in the digestive system, to correct an imbalance known as dysbiosis.
This rebalancing is believed to decrease the production and accumulation of certain amino acids, such as phenylalanine and isoleucine. In mouse models of Alzheimer’s, higher levels of these amino acids were associated with the activation of pro-inflammatory immune cells. These inflammatory cells can then travel to the brain, contributing to neuroinflammation.
By suppressing this gut dysbiosis, sodium oligomannate may reduce this source of inflammation. This action is hypothesized to lessen the activation of the brain’s immune cells, known as microglia, and decrease the chronic neuroinflammation that damages neurons. This approach marks a departure from many Alzheimer’s therapies that directly target amyloid plaques in the brain.
Clinical Trial Evidence
The primary evidence for sodium oligomannate’s effectiveness comes from a Phase 3 clinical trial conducted in China. This multicenter, randomized, placebo-controlled study assessed the drug’s impact on cognitive function over a 36-week period in patients with mild to moderate Alzheimer’s disease.
The main measure for efficacy was the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), which evaluates memory, language, and praxis. The results of the Phase 3 trial indicated that the group receiving sodium oligomannate showed a statistically significant improvement in their ADAS-Cog scores compared to the placebo group.
This trial met its primary endpoint, suggesting a therapeutic benefit in slowing cognitive decline. The positive trend was also seen in an earlier Phase 2 trial, where a 900 mg dose showed greater improvement on the ADAS-Cog12 score compared to placebo.
Regulatory Status and Scientific Reception
In November 2019, China’s National Medical Products Administration (NMPA) granted conditional approval for sodium oligomannate for the treatment of mild to moderate Alzheimer’s disease. Following this, the developer, Green Valley Pharmaceuticals, announced plans for a global multi-center clinical trial to seek approval in other countries.
In April 2020, the U.S. Food and Drug Administration (FDA) gave clearance for an Investigational New Drug (IND) application. This allowed the planned “Green Memory” trial to proceed, which was set to take place in 200 sites across 14 countries. However, the company later announced the discontinuation of these global trials, citing challenges related to financing.
The international scientific community has expressed a mix of interest and skepticism. Some researchers have called for more extensive and independently verified data to fully understand the drug’s effects and confirm the findings from the initial Chinese trial. The debate highlights the need for further research into modulating the gut microbiome for neurodegenerative diseases.
Administration and Safety Profile
Sodium oligomannate is administered as an oral capsule, with a 900 mg daily dosage tested in later trials. This method is convenient for patients compared to treatments requiring infusions.
The drug was well-tolerated in clinical trials. The most common adverse events were mild gastrointestinal issues, consistent with a drug acting within the gut. Overall, treatment-related adverse event rates were comparable between the sodium oligomannate and placebo groups.