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China conditionally approves drug derived from brown algae for Alzheimer's disease
Here is part of the story:
China’s National Medical Products Administration granted conditional approval to the drug Oligomannate (GV-971), the regulator said in a statement on its website.
Shanghai Green Valley Pharmaceuticals said in a separate statement the drug received the regulator’s approval for treatment of "mild to moderate Alzheimer’s disease and improving cognitive function," following a Phase 3 clinical trial in China.
“Trial results demonstrated that Oligomannate statistically improve cognitive function in mild-to-moderate AD patients as early as week 4 and the benefit was sustained at each follow-up assessment visit,” the company said.
It said it expects the drug to be available in China by early 2020 and plans to apply for marketing authorization in "selected countries following the China launch." It plans a multi-center global Phase 3 clinical trial with sites in the U.S., Europe and Asia starting early next year to support those filings.
The drug is a low molecular acid oligosaccharide compound extracted from marine brown algae, according to the Chinese regulator’s statement. The regulator said it requires further studies on the drug’s pharmacology, safety and effectiveness after it’s launched to the market.
I have been looking for a mechanism of action for this drug and this is the best that I have found so far:
Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO) on lipopolysaccharide (LPS)/β-amyloid (Aβ)-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to LPS/Aβ stimulation led to a significant inhibition of production of nitric oxide (NO) and prostaglandin E₂ (PGE₂), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and secretion of proinflammatory cytokines. We further demonstrated that AdO remarkably attenuated the LPS-activated overexpression of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB in BV2 cells. In addition to the impressive inhibitory effect on neuroinflammation, we also found that AdO promoted the phagocytosis of Aβ through its interaction with TLR4 in microglia. Our results suggested that AdO exerted the inhibitory effect on neuroinflammation and the promotion effect on microglial phagocytosis, indicating its potential as a nutraceutical or therapeutic agent for neurodegenerative diseases, particularly Alzheimer's disease (AD).
Inhbiting inducible nitric oxide synthase also inhibits the formation of peroxynitrite which is likely responsible for much of the damage done to the brain in Alzheimer's disease.
Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased beta-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD.
Maybe this actually works.
A link to the trial results:
Better yet in terms of mechanism:
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...
China has approved seaweed-based drug called Oligomannate to treat mild to moderate Alzheimer’s and improvement can be seen in cognitive function in as little as four weeks.
Seaweed is a standard in Asian cuisine, available at health food and bulk food stores. A tad salty.
So I was reading about early travels to Asia to buy spices, yet I don't think I actually use those spices in everyday life. The first medicines were...food.
In the Alzforum article, if you look at the graph of the test scores, both the treatment and placebo groups improved up to 24 weeks, but then between 24 weeks and 36 weeks, the treatment group improved and the placebo group declined. Why did the improvements and declines occur in the same time interval? The improvements weren't great but they were statistically significant.
I have to wonder how carefully the Chinese government is supervising this trial. If this treatment were trialed by the FDA in the US and by governments in Canada and the EU, would they come up with simular positive results? Time will tell.
I don't think this drug can be legally imported into the US without going through a FDA clinical trial unless the FDA makes a special exception. Meanwhile expect to see a lot of all-natural seaweed products claiming to be just like this drug popping up in health food stores everywhere. Who knows what they will contain?
The FDA has approved a phase three clinical trial for GV-971 (sodium oligomannate). The results unfortunately won't be known until 2025.
Shanghai Green Valley Pharmaceutical Co. got clearance on April 8 for the U.S. part of a global trial that seeks to enroll more than 2,000 patients with mild-to-moderate Alzheimer’s across North America, Europe and Asia, according to a company statement Sunday...
FDA’s move to let Green Valley go straight to late-stage large-scale trials is a boost to its bid for global legitimacy after the experimental drug oligomannate received conditional approval in China late last year. It’s the first new medicine for the incurable neuro-degenerative disorder in nearly 17 years but there’s been skepticism from researchers over its unusual approach and efficacy
Global drugmakers have invested billions of dollars in over 190 experimental drugs to treat Alzheimer’s, which affects 10 million people in China and 5.8 million in the U.S., with little to show for it...
The trial will be conducted for a year during which neither investigators nor patients will know who’s been given the medicine and who’s on placebo to avoid bias when interpreting results. This will be followed by six months of open study when all the patients will receive the drug...
The trial will be conducted for a year during which neither investigators nor patients will know who’s been given the medicine and who’s on placebo to avoid bias when interpreting results. This will be followed by six months of open study when all the patients will receive the drug.
Oligomannate’s unusual method of slowing down Alzheimer’s has been controversial as it still lacks sufficient evidence in human studies. The drug aims to readjust the microbiome in the gut, which Green Valley says ultimately leads to reduced neuron inflammation in the brain, thus slowing the progression of the disease.
The approach breaks from the pack: in their efforts, global drugmakers like Roche Holding Ag and Biogen Inc. have focused on a protein called beta amyloid, which forms clumps of plaque in the brain and is thought to be a cause of the disease. But a lack of progress has led to calls from researchers to rethink the industry’s fixation on beta amyloid.
It's nice to see that drug developers are looking beyond amyloid. There is plenty of evidence that the gut-brain connection is valid.
While there is a certain amount of doubt about results out of China right now,
Any company and any country COULD fake their study results - but any party that does that is risking their reputation, and their future profits. Ultimately, every study is repeated several times by multiple other parties, so the results will out in the end.
Let's try to put our bias to the side and look at the data and the mechanism of action .Does it make sense? Reducing bacteria, causing a reduction in inflammation seems pretty feasible.
These boards have anecdotal evidence that the use of antibiotics has improved cognition remarkably. Just because the results are good, doesn't mean they aren't real.
I agree. Some people dismiss anecdotes and small-scale clinical trials out of hand. Some may not pan out, but other might. If we don't ever study them further we will never know.
Certain antibiotics and probiotics may be good for both the gut and the brain. Part of the damage done to the gut also can then occur to the brain. Some of the damage done to the brain likely occurs independently of damage to the gut. It is possible that certain compounds (including those in brown seaweed) may help the gut and the brain both in a dependent and independent fashion.