GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities

CNS Neurosci Ther, 2024 · DOI: 10.1111/cns.14847 · Published: June 25, 2024

Simple Explanation

This study investigates the potential of GV-971, a drug used for Alzheimer's disease, to treat neuromyelitis optica spectrum disorders (NMOSD) by targeting the gut-brain axis and reducing neuroinflammation. The researchers used mouse models of NMOSD, inducing the disease through specific injections and techniques, to observe the effects of GV-971 on disease progression, symptoms, and overall health. The study found that GV-971 significantly reduced the incidence and severity of NMOSD in mice, alleviated neuroinflammation and injury in the spinal cord, and improved imbalances in gut microbiota, peripheral inflammation, and metabolic disorders.

Study Duration

Not specified

Participants

Mice (aged and young, female C57BL/6)

Evidence Level

Not specified

Key Findings

1
GV-971 significantly reduces the incidence of NMOSD, alleviates symptoms, and prolongs survival in NMOSD mouse models.
2
GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders.
3
GV-971 has the capacity to remodel the composition of the gut microbiota, which were parallel with the alleviation of neuroinflammation.

Research Summary

The study established NMOSD animal models in both aged and young mice using the EAE model, observing a higher disease incidence and elevated clinical scores compared to the EAE model alone. GV-971 treatment resulted in a significant reduction in disease incidence and clinical symptoms, as well as an extension of survival time for NMOSD-afflicted aged mice. The study found that GV-971 significantly remodeled the gut microbiota, reduced peripheral inflammation and metabolic disorder, and alleviated neuroinflammation in the spinal cord.

Practical Implications

Therapeutic Potential

GV-971 shows promise as a treatment option for NMOSD, particularly for long-term maintenance therapy after initial immunosuppressant and glucocorticoid treatments.

Gut-Brain Axis Target

The study supports the concept of targeting the gut-brain axis for NMOSD treatment, suggesting that modulating gut microbiota can reduce neuroinflammation and improve outcomes.

Metabolic Remodeling

GV-971's ability to remodel metabolic profiles in NMOSD models indicates its potential to restore metabolic homeostasis and mitigate disease progression.

Study Limitations

1
The mechanistic study of causal relationships between gut microbiota, peripheral inflammation, metabolites, and neuroinflammation remains insufficient.
2
Understanding how GV-971 regulates gut microbiota and reduces peripheral inflammation and metabolites to mediate its suppression of neuroinflammation remains a challenge.
3
The genera influenced by GV-971 in the NMOSD model differ from those observed in previous AD models.

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