Seaweed preparation GV-971 slows progression of NMOSD in mice
Findings support idea that gut microbiota, gut-brain axis play a role in disorder
A seaweed-derived preparation named GV-971 (sodium oligomannate) that has anti-inflammatory effects through the gut-brain axis, delayed the onset and progression of neuromyelitis optica spectrum disorder (NMOSD) in mouse models of the disease, a study shows.
The preparation developed by Green Valley Pharmaceuticals is approved in China as an oral capsule to improve cognitive function in people with mild to moderate Alzheimer’s disease. It’s thought to work by restoring unbalanced gut microbiota, that is, the collection of microorganisms in the gastrointestinal system, thereby reducing the disease-driving inflammation that spreads from the gut to the brain.
The findings further support the idea that gut microbiota and the gut-brain axis play a role in NMOSD, and that therapeutic approaches like GV-971 could benefit this patient population.
The study, “GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities,” was published in CNS Neuroscience & Therapeutics.
Changes in gut microbiota have been linked to NMOSD, an inflammatory autoimmune disease that most often affects the eye nerves and spinal cord. The underlying mechanisms of this link aren’t clear, but it’s thought that an unbalanced gut microbiota produces more of certain molecules that may prime immune cells to mount inflammatory responses.
Effects of GV-971 in NMOSD mice
GV-971 is a mixture of short chains of sugar molecules, or oligosaccharides, isolated from marine brown algae. The mixture, cleared for use in China for Alzheimer’s patients, has been shown to reduce neuroinflammation in Alzheimer’s mouse models by changing the gut microbiota’s profile.
Building on this, Green Valley researchers and their colleagues evaluated how well GV-971 works in two NMOSD mouse models they developed.
Aged mice with experimental autoimmune encephalomyelitis — a model that mimics multiple sclerosis, another inflammatory neurodegenerative disease — were injected NMOSD patient-derived antibodies against the AQP4 protein, the most common NMOSD-driving self-reactive antibodies.
Control mice were injected antibodies from healthy people. Both groups were given a daily dose of oral GV-971 or methylprednisolone, a corticosteroid used to reduce inflammation in NMOSD.
Results in the aged mouse model showed that after 16 weeks, or about 3.5 months, 90% of the untreated mice developed NMOSD symptoms compared with 70% of those given GV-971 and 10% of those treated with methylprednisolone. At the last follow-up, all the untreated animals, 90% of the GV-971-treated animals, and 70% of those given methylprednisolone developed the disease.. Differences between the untreated and treated groups were statistically significant.
Moreover, the mice in both treatment groups showed significantly less severe NMOSD symptoms relative to the untreated mice, as reflected by lower scores on a 6-point clinical scale. GV-971 and methylprednisolone also slowed weight loss and increased survival rates, with the steroid generally having more profound effects.
A young mouse model was created with somewhat similar methods and GV-971 was also shown to significantly reduce the rate of NMOSD development — to 40% — and result in significantly less severe symptoms.
Further analyses showed GV-971 both lowered inflammation and nerve fiber damage in the spinal cord, and helped balance gut microbiota by restoring its composition to one that resembled a healthy gut. This suggests the therapy may break the harmful cycle of inflammation and changes in the composition of gut bacteria that contribute to neuroinflammation in NMOSD.
The findings showcase the importance of gut health in neurological diseases and open up new possibilities for treatments that target the gut-brain connection.
GV-971 “as a treatment option for NMOSD holds considerable therapeutic promise, particularly for long-term maintenance therapy following immunosuppressant and glucocorticoid treatments,” wrote the researchers, who said further studies should explain how GV-971 works on NMOSD and evaluate its “therapeutic potential in clinical settings.”
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