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Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
Something to watch...
You may well not have heard of Green Valley — which was founded in 1997 to develop carbohydrate drugs and headquartered in Shanghai’s buzzing Zhangjiang Science City — but they have allied themselves with some familiar names for this Alzheimer’s program. IQVIA and Signant Health (formerly Bracket) were two of the CROs engaged in the Phase III program supporting the OK, and Eric Reiman — executive director of Banner Alzheimer’s Institute, which has been involved in key studies — is a scientific adviser alongside renowned researchers Jeffrey Cummings and Philip Scheltens.
Here’s how Meiyu Geng a professor at Shanghai Institute of Materia Medica and inventor of the drug, and her team described the mechanism of action in a Nature Cell Research paper about their preclinical work:
We have revealed that gut microbiota patterns and amino acid-derived metabolites are important for the infiltration of specific types of immune cells, which drives neuroinflammation during AD progression. GV-971 therapeutically harnesses the abnormal production of amino acids, infiltration of immune cells to the brain, and in turn neuroinflammation via remodelling the gut microbiota.
Research paper noted: https://www.nature.com/articles/s41422-019-0216-x
I finally feel we are getting some place with the treatment of Alzheimer's disease.
The hypothesis is that inflammatory cells and amyloid oligomers in the gut make there way to the brain causing Alzheimer's disesae:
Amyloid precursor protein that forms amyloid beta plaques in AD is normally expressed in the ENS by gut bacteria, but when amyloid beta accumulates, it compromises CNS functions. Escherichia coli and Salmonella enterica are among the many bacterial strains that express and secrete amyloid proteins and contribute to AD pathogenesis. Gut microbiota is essential for regulating microglia maturation and activation, and activated microglia secrete significant amounts of iNOS. Pharmacological interventions and lifestyle modifications to rectify aberrant NO signaling in AD include NOS inhibitors, NMDA receptor antagonists, potassium channel modulators, probiotics, diet, and exercise.
There are a couple of problems with this hypothesis--first amyloid and inflammation are rarely the first trigger for the disease. Pesticides for example can damage both the gut-blood barrier and the blood-brain barrier. Secondly, there are other routes to Alzheimer's disease besides the gut: air pollutants through the nose, for instance.
What leads to amyloid, inflammation, and brain damage is oxidation and nitration and that is why the compound derived from brain algae is likely effective.
Alginate oligosaccharide (AOS) has recently demonstrated the ability to protect against acute doxorubicin cardiotoxicity and neurodegenerative disorders by inhibiting oxidative stress and endoplasmic reticulum (ER) stress-mediated apoptosis...With regard to mechanism, AOS pretreatment markedly attenuated nitrative/oxidative stress, as evidenced by decreases in 3-nitrotyrosine content and superoxide generation, and downregulated inducible nitric oxide synthase...