Skip to main content
Menu

Alzheimer's Disease

More, Unfortunately, on the Chinese Alzheimer’s Drug Approval

I wrote yesterday about the surprise decision by the Chinese regulators to allow a new Alzheimer’s drug on the market. That drug (GV-971) was developed by Green Valley Pharmaceuticals, a company (and a drug, for that matter) that frankly I had never heard of. But other people have heard of both, and they’ve been contacting me about it. This information warrants a follow-up post.

First off, I mentioned that I was having trouble finding the Phase II data. Well, here’s a summary of it, or at least some of it, and you know what? This compound did not appear to reach statistical significance versus placebo. Not in the trial shown. Why, you wonder, was it progressed to Phase III in the first place? And as mentioned yesterday, it’s not like we have (so far) enough data to evaluate that later trial itself.

However, there is a file going around (especially around Chinese social media), a set of audience photographs (you can see the back of someone’s head in the bottom of the frame) of the presentation given on the drug at the 2019 China BioMed Innovation and Investment Conference, which took place in late September in Suzhou. These slides contain a great deal more information, and some of this was at one point more publicly available on the company’s web site, but seems to have been removed (according to a correspondent of mine this morning).

Here’s a key slide, and the source of that 2.54-point improvement in the ADAS-Cog scores mentioned in the company’s press release. One notable feature is the steep drop in the scores of the placebo group between week 24 and week 36, which is rather strange, and for which no explanation is apparently given. And if I’m interpreting this correctly, both the placebo and treatment groups improved at the earlier time points, it’s just that the treatment group improved more? The same drop in the placebo group is seen in the company’s slide presenting data on the MMSE rating scale. The larger Phase III that’s planned will be of great interest, for sure.

Edit: I want to call attention to this comment, from a researcher in the microbiome field, who has trouble making sense of the recent paper’s data. His opinion is that their results are not consistent with their proposed mechanism of action – I would be very interested in hearing further discussion on this as well!

Moving on to Green Valley itself, AndyBiotech on Twitter has noted that the company has been in regulatory trouble before. This CCTV report from 2007 (there are others) goes into detail (Google Translate needed, unless you’re a Chinese speaker). Their 绿谷灵芝宝  product, Shuangling Guben San (formerly known as Zhonghua Lingzhibao) prepared from the Lingzhi fungus (Ganoderma lucidum, a well-known component of Chinese traditional medicine) has been the subject of many stories in the Chinese press and internet, especially in the 2007-2008 period, but very little of this has ever appeared on the English-language web. It seems to have been marketed (numerous times, over a period of many years) as some sort of cancer cure, with claims on Chinese social media posts such as “It has successfully helped 1.6 million cancer patients in the past 13 years“, which attracted the attention of law enforcement. They’re not the only ones using this ingredient (here’s a Cochrane review on the subject of the fungus, which not surprisingly comes down on the “insufficient evidence” side), but they seem to have been particularly aggressive with their claims  and advertising (some sort of proprietary processing that supposedly gave it dramatic potency). This led to lawsuits from patients and customers and exposés in the Chinese media.

If someone more familiar with the history of Green Valley can speak to how what is apparently the same company can now plausibly come forward with an Alzheimer’s drug candidate after such a history, I would be very interested to hear about it. Has there been some sort of major shakeup in management and company behavior? Or are these the same people?

Now for the most recent paper on GV-971. It was noted in the comments section of yesterday’s blog post that its authors have a number of comments in PubPeer on their past work. The paper’s lead author is Meiyu Geng, of the State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, of the Chinese Academy of Sciences. Unfortunately, the comments on other papers from this lab detail what appear to be clear instances of image duplication and overlap in what are supposed to be completely different experiments and samples. There is a lot of that going around, of course, but it’s never right and it’s never a good sign.

So overall, I am even less thrilled than I was yesterday about the prospects for this drug. A new Alzheimer’s therapy is already going to face a tough development path and a lot of skepticism, but this one has even more red flags than I had realized yesterday. More on this as it develops. But it’s not developing well.

47 comments on “More, Unfortunately, on the Chinese Alzheimer’s Drug Approval”

  1. forwardslashs says:

    How long until the usual excuse of ‘this data manipulation was done by post-doc x or PhD student y and I had no knowledge’ excuse?

    1. TigerBB8 says:

      Just did. ” …errors were introduced into our manuscript during the stage of figure preparation by the first author unintentional mistakes.”
      https://pubpeer.com/publications/BA4F874D9B9496B305B0C23376B52B#7

  2. Another Guy says:

    Looking at the slide, each data point shows no overlap between the confidence intervals, so at a first approximation, it would seem that the seaweed group attained statistical superiority, and at week 4. That’s some special seaweed!

    1. Skeptical says:

      The error bars also seem unusually small and consistent from timepoint to timepoint.

  3. John Wayne says:

    Oh, so it works as well as Biogen’s clinical candidate. That is too bad.

  4. EY says:

    Reminds me of Dimebon, which had positive data in one country (Russia) and was subsequently negative in multinational Phase 3 trials by Medivation and Pfizer. The MOA didn’t seem compelling at the time Phase 3 was started.

    1. luysii says:

      EY — ah yes Dimebon. Such pseudoresponses cause a lot of pain. The wife of a classmate (now dead of Alzheimer’s) moved heaven and earth to get Dimebon when the hype came out. It didn’t work, and (I think) she spend a lot of money getting it.

  5. sgcox says:

    Oh, Barbara Streisand effect in action again.

    1. David E. Young, MD says:

      Barbra

      1. tally ho says:

        “Babs” for short

  6. Andre Brandli says:

    I am afraid that this story going to turn out to be massive hoax and it will tarnish the reputation of the China’s National Medical Products Administration (NMPA) profoundly. This at a time, when China is aspiring to be come a drug developing nation on par with Western nations.

    The facts about oligomannate known to date are just not very encouraging. For the following reasons:
    1) The preclinical studies were performed with an inadequate mouse AD model. The 5xFAD model is widely used despite the fact that it’s completely artificial as no human patients are known to carry 5 different pathogenic FAD genes.
    2) The mechanism of action is completely unknown. Does it prevent or stop amyloid plaque build up? Does is dissolve plaques? Does it reduce neuroinflammation? How is it thought to modulate the microbiome of AD patients?
    3) Only one (ADAS-cog) of four clinical endpoints showed an effect compared to placebo. In ADAS-cog, a possible effect is only really event at the last data point, 36 weeks of treatment. Here the effect can be largely be attributed to the placebo patients suddenly experiencing a cognitive decline.
    4) The clinical trial of 36 weeks is definitely far too short to be convincing. AD trials typically run for 2 years or longer.
    5) As pointed out Green Valley Pharmaceuticals has in the past had a problem with selling a cancer drug with unproven therapeutic efficacy.
    6) Green Valley claims that the manuscript reporting the outcome of the AD trial is under review by NEJM. I bet that the paper will never see its light in NEJM.

    My take is that this is all a huge scam. Sounds to me like a huge conspiracy to make money with snake oil. Heads will be rolling at NMPA sooner or later.

    1. A nony mouse says:

      Yes I have to agree. Frauds unfortunate are not uncommon they are everywhere. I think the real astounding story will be that the Chinese regulatory authorities approved this mess.

      1. loupgarous says:

        Curious if someone’s going to bat for Green Valley in the Chinese Politburo. Derek’s discussed China’s decision to not only waive safety and efficacy testing requirements for, but to censor criticism of “traditional Chinese medicine” therapy, even throw people in jail for such criticism.

        We could see sort of a “Orrin Hatch/Tom Harkin on steroids” effect with China’s officialdom doubling down on their support for this unconventional Alzheimer’s therapy if there’s strong official support for Green Valley despite all the irregularities surrounding GV-971’s development.

        On the other hand, Derek has also discussed progress toward reform in Chinese science, so backpedaling of the sort we saw after He Jiankui’s unauthorized experiment in trying to knock CCR5 out of the cells of human fetuses might happen.

        An old Chinese curse goes “May you live in interesting times.” The Chinese biomedical sector seems to be accursed in that way lately.

        1. metaphysician says:

          Wild guess time: someone high in the Chinese government is concerned about their vast population, and the costs as they age. Officially supporting and encouraging TCM helps keep that in check by reducing the average lifespan.

          1. loupgarous says:

            That fits with something P.J. O’Rourke (whose day job is now H.L. Mencken Research Fellow with the Cato institute) reported hearing from a Chinese government official who asked him about our Social Security program. The Chinese official asked O’Rourke if retirement benefits such as SS didn’t encourage laziness in the workforce.

            It’s also eerily reminiscent of former Obama administration bioethics adviser Ezekiel Emmanuel’s Atlantic article “Why I Hope to Die at 75”.

  7. Lane Simonian says:

    The usual decline in Adas-cog scores between 24 weeks and 36 weeks is between 1 and 2 points so the placebo decline is somewhat higher in this trial. You usually see a 2.5 point change in the placebo group between 6 months and 12 months.

    https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2b1b7b5f-2f20-418c-b1ac-794c2ef1ce5e&type=display

    In at least one Aricept trial the drug group improved slightly more than the placebo group early on, so this is not particularly unusual either.

    https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2b1b7b5f-2f20-418c-b1ac-794c2ef1ce5e&type=display

    Some other significant points, perhaps, few if any of the participants in this trial were on other Alzheimer’s medications and the trial was for mild to moderate Alzheimer’s disease. Anti-amyloid drugs only appear to slow down the rate of decline in APOE4 carriers and only during the early stage of the disease.

    https://www.ncbi.nlm.nih.gov/pubmed/29199323

    https://www.alzforum.org/news/conference-coverage/second-look-ban2401-data-still-positive-despite-snafu

    The other criticisms and information are valid and concerning. The big question, though, is does the trend line continue or does this drug drop off like Aricept over a much longer trial.

    1. Ian Malone says:

      With respect to Derek’s, “And if I’m interpreting this correctly, both the placebo and treatment groups improved at the earlier time points, it’s just that the treatment group improved more?” this is not unheard of with psychology tests, there’s a practice effect which can cause score to go up after the first assessment. (We actually get participants come in and tell us how they’ve been practicing, which isn’t what practice effect means, but still…) You’d expect this to be greater with short intervals, and hope it will come out in the wash as the control group declines anyway while your treatment group is spared further decline.

      Donepepzil (trade-name aricept, prescribers take note…) seems to function by providing an offset to some of the effects of disease, which you might expect from its mechanism of action, making more neurotransmitter available and so alleviating symptoms a bit, but doing nothing about disease process or long term decline. (Other than you can view boosting function above where you’d otherwise be by a certain amount as equivalent to delaying decline to a certain point by some amount of time, if you can maintain the effect.) If, and that’s a 50 metre high IF carved in granite, this stuff actually did anything, my money would be on it being of the same nature, as this study seems a bit too short to be looking at functional decline. But I think I’ll not be wagering anything on this one.

  8. ??? says:

    So, if all this information comes out here in a couple of days… how come the Chinese FDA approved this drug? Did they not have access to it?

    1. loupgarous says:

      Even FDA makes a few head-scratching NDA decisions (think about the approval of Sarepta).

      We’ll have to see whether China’s regulators stand by their decision to approve GV-971 or not, and what reasons they offer. Not sure we’ll ever learn who knew what during the Chinese approval process. FDA’s painstakingly transparent compared to regulators from some other countries.

      1. loupgarous says:

        Whoops. That ought to have been FDA’s “approval of Exondys (eteplirsen)” granted to the firm Sarepta, after a heartstring-plucking PR offensive and a comment about Sarepta’s share price offered in partial explanation of the approval decision.

    2. G. White says:

      obviously you dont know anything about Chinese FDA. The former agency chief was sentenced to death for taking bribes and giving away approvals which caused many death.

      This is fabricated result, i would bet my arm for it.

  9. Chairman Mao says:

    No molecule survives the ITP Inquisition! From now on any new drugs from any country have to be approved here before any regulatory agencies. Even more important is that regulatory agencies for new drugs must be approved by In the Pipeline!

    Lets stop messing around with these amateurs.

    1. loupgarous says:

      Hey, no one forced Green Valley or China’s drug regulators to make the judgment calls they did. At least they didn’t claim GV-971 is traditional Chinese medicine. If they had, many of us could have wound up on China’s “most wanted” list.

  10. Chrispy says:

    I am shocked, SHOCKED I tell you.

    This drug discovery thing is hard enough without all manner of hucksters trying to pawn off the next Great Cure. I can’t even open a newspaper anymore without being regaled by stem cell treatments and bee pollen mumbo jumbo.

    1. John Wayne says:

      It does seem a lot easier to sell things that don’t have to work. I think we’ve all thought about quitting objective science and starting an organic all natural nonGMO snake oil shop (or, in New England, shoppe.)

      “I’m a former industry insider here to tell you that they are hiding the cures from us all to make money! I have put together secret knowledge from big pharma, big agriculture and the government to tell the truth. This stuff really works, and they don’t wan’t you to know about it! Click to the right to order your own supply of (insert product and what it cures) from my staff of dedicated truth seekers. Today only, you get a 20% discount for placing a six month order. All natural cures for all natural people.”

      At least the placebo I would sell is safe.

  11. Magrinho says:

    Yu Hua wrote an excellent book on daily life in China called “China in Ten Words” in with each chapter focuses on a particular word/theme to describe modern China. The last chapter is entitled “Bamboozle” and it describes a modern China that is struggling to find its way ethically and morally amid widespread fakery and deception at all levels. Some of the stories are funny but many are terrifying and sad.
    The Green Valley Pharma story could have been lifted straight from the book.

    1. Another anon says:

      Agreed, this was a great book!

    2. david says:

      ” . . . that is struggling to find its way ethically and morally amid widespread fakery and deception at all levels.” Sure glad we don’t have that problem here is the US!

  12. exGlaxoid says:

    This is one of the first useful articles about Alzheimer’s I have seen in a while. Hopefully it will be more helpful than Chinese meds.

    https://www.sciencemag.org/news/2019/11/colombian-woman-s-genes-offer-new-clues-staving-alzheimer-s

    https://news.yahoo.com/why-didnt-she-alzheimers-answer-200846677.html

    1. Ian Malone says:

      Indeed, this is pretty interesting. I’ll bet* there are people now combing through databases to see what the prevalence of this mutation in AD cohorts is. (Of course, being rare, we probably don’t know its prevalence in the population(s) at large.)

      * re. other comment, on this one I would actually bet.

      1. Harrison says:

        What’s interesting to me is that a protective variant of apoE, the number 1 genetic risk factor for sporadic AD, is limiting pathology in familial Alzheimer’s disease, and putatively doing so through effects on tau biology (as opposed to amyloid). We’ve known about apoE4 for 25 years, but it’s mechanism is not well understood and has been severely under-studied compared to amyloid biology.

  13. C_B says:

    These fools have failed Step 04 of the “successful science fraud” process, “don’t do research anyone cares about.”

    They should have read the guide: https://arstechnica.com/science/2012/07/epic-fraud-how-to-succeed-in-science-without-doing-any/

    1. Churlish says:

      Thanks for that wonderfully witty and depressing link!

    2. Eugene says:

      Succintly captures the the steps for fraudulent research, as dissected on this blog numerous times. Extra points for the using the artwork from the 1950’s Gilbert Atomic Energy Lab, when kids could do real science!

  14. Surfactrant says:

    At CTAD in Beijing this year, GV proposed a biome based mechanism of action.

    Stating GV-971 …

    1) tl:dr – reconditions the dysbiosis of gut biome
    2) specific action affected only rTg4510 mice and not WT mice.
    3) breaks “microbiota-immune cell link in 5XFAD mice”.
    4) inhibits infiltration of peripheral immune cells into the brain
    5) inhibits M1 type microglial activation in 5xFAD mice
    6) reduces cytokine in 5xFAD mice
    7) Tg fecal bacteria induced elevation of Th1 cells, Tg fecal bacteria treated decreased elevation
    8)similar (to 7) effects observed in APP/PS1 mice – effect eliminated by anitbiotics

    I think my biome gets triggered whenever hearing of biome used as justification!

  15. Hocus Pocus says:

    Cure for Alzheimer’s forgotten

  16. aairfccha says:

    Somewhat related: Guardian – Doctors call for tighter control of traditional Chinese medicine

    https://www.theguardian.com/education/2019/nov/06/doctors-europe-call-for-tighter-control-of-traditional-chinese-medicine
    “[…] The Federation of European Academies of Medicine (FEAM) and the European Academies’ Science Advisory Council will issue a joint statement on Thursday urging the WHO to clarify how traditional Chinese medicine and other complementary therapies should be used. […]”

  17. Lane Simonian says:

    A more brain specific mechanism for alginate oligosaccharides, at least early in Alzheimer’s.

    https://www.ncbi.nlm.nih.gov/pubmed/21543116

    https://www.ncbi.nlm.nih.gov/pubmed/16141213

    1. AlloG says:

      So dat means we should be eating agar to stop my brain from deteriorating?

      It could be too late.

  18. autumn says:

    @loupgarous
    Sprout Pharma used politics to get its drug approved.
    https://www.thecut.com/2016/09/how-addyi-the-female-viagra-won-fda-approval.html
    https://www.cnn.com/2019/05/08/health/women-libido-addyi-partner/index.html

    https://www.prnewswire.com/news-releases/even-the-score-fda-approval-of-first-ever-medical-treatment-option-for-hsdd-is-game-changer-for-women-300130406.html
    18 members of Congress […] including 11 members urged the FDA “to continue your focus on providing women with safe and effective treatments they need and deserve.” Last year, four Congresswomen voiced their concerns about the lack of sexual dysfunction treatment options for women. Leaders from the National Organization for Women, the National Consumers League, the International Society for the Study of Women’s Sexual Health, the Memorial Sloan-Kettering Cancer Center and the Center for Health and Gender Equity, among others, also penned letters to the FDA raising similar concerns with the FDA’s failure to provide treatment options to women struggling with sexual dysfunction.
    Names of these Congressmen and women are not as easy to find now that the Even The Score website is defunct.

    Despite his good intention after the death of his teen son, ex-Congressman Bart Stupak’s interference in the FDA approval process of acne-related products were misguided at times but I did not find articles related to this. Background articles:
    https://dash.harvard.edu/bitstream/handle/1/8963867/Green.html?sequence=2&isAllowed=y
    https://www.cbsnews.com/news/roches-accutane-suit-over-death-of-congressmans-son-nixed/
    “Stupak used his political position to pressure FDA and Hoffmann-La Roche to increase regulation of the Drug. It was Stupak who pushed the company to create an informed consent form and medication guide for patients; on Stupak’s urging Hoffmann-La Roche also terminated advertisements aimed at minors.”

    There had been some FDA approvals that relied on data-mining rather than efficacy, which makes ICER’s evaluations helpful in my opinion.

    @Chrispy @John Wayne
    https://khn.org/news/elite-hospitals-plunge-into-unproven-stem-cell-treatments/
    Mayo Clinic, the Cleveland Clinic, the University of Miami, Swedish Medical Center in Seattle.
    Not mentioned in this article is that there are at least over 700 known fradulent stem cell clinics this year.

    https://khn.org/news/india-burgeoning-chronic-pain-market-us-drugmakers-stand-to-profit/
    “Beset By Lawsuits And Criticism In U.S., Opioid Makers Eye New Market In India”
    J&J fentanyl patch, Abbott Lab’s tramadol, Sackler-related Mundipharma products are in India

    Can US media’s attention on China be slightly disproportional compared to the rest of the world?
    https://www.reuters.com/article/us-kobe-steel-scandal-quality-analysis/kobe-steel-scandal-latest-to-expose-made-in-japan-fault-lines-idUSKBN1CI25N
    Nissan, Suzuki, Mitsubishi, Takata, Toyo Tire, Asahi Kasei also have industrial scandals

    https://retractionwatch.com/the-retraction-watch-leaderboard/
    Among the top 10 leaders, Yoshitaka Fujii, Yoshihiro Sato, Jun Iwamoto, Yuhji Sato’s total retracted papers exceeded all the other researchers from all the other countries combined.
    There is also the suicide scandal of Yoshiki Sasai of Riken Center. One of Sasai’s colleagues also faced a non-reproducibility issue. Japan accounts for 4% of world scientific research. This leadership looks disproportionately high. With the headlines on Researching While Chinese and industrial espionage, I read “Friendly Spies” by Peter Schweizer. There are Mitsubishi, Matsushita, Fujitsu on its Fairchild Semiconductors saga, Hitachi on IBM espionage conviction. Hitachi appeared 147 times in the book. Starting from page 18, and still going by page 309. Page 38 mentioned agents operating out of the consulate office in San Francisco. The book referred to the Japan’s former Institute of Industrial Protection as an industrial espionage school, and that Matsushita’s intelligence operation took up two floors of a Manhattan skyscraper, quasi-official Japanese External Trade Organization used as an intelligence asset, and the Japanese ministry for International Trade and Industry served as the hub of this network. Page 74, By 1956, MITI established a systematic arrangement for sending businessmen overseas, establishing a rule that no fewer than ten thousand persons would be sent abroad per year-principally to the United States-to bring back technology.
    Are most of you familiar with all these already? How well-known was this in the 1980s back when the Mitsubishi IBM drama was playing out?

    A search on this website showed a handful of dubious papers related to Shanghai Institute of Materia Medica but none from Geng Meiyu
    http://retractiondatabase.org/RetractionSearch.aspx?AspxAutoDetectCookieSupport=1

    https://www.axios.com/hospitals-drug-prices-trump-pharma-223585c8-f085-454d-8e17-078177274d24.html
    https://www.beckershospitalreview.com/legal-regulatory-issues/uhs-execs-directors-escape-lawsuit-over-billing-practices.html

    I sometimes don’t understand the focus of US media coverage. Is the amount of media attention proportional to the gravity of the issue at hand? I rarely ever came across any of the above news from reading regular news headlines. Business, economic, political news coverage is even more uneven than the more science-based ones.

    Which websites have more complete coverage of science and healthcare news in one place?

    1. None says:

      Alzheimer’s disease is one of the hottest fields in medicine right now and there is so much scrutiny everywhere. There have been so many very high profile attempts and failures. The international attention is driven really by this situation. Look at the attention given to Biogen’s recent results.

      If it is really a scam you have to question the situational awareness of the Chinese regulatory authorities. Either they didn’t realize this would be a huge story (not a good look) or they didn’t care (not a good look).

  19. Liping Zhao says:

    This is Liping Zhao. I am a microbiome researcher, who has one lab in Shanghai Jiao Tong University and one at Rutgers University.

    Out of curiosity, I read the pre-clinical Cell Research paper on how GV-971 modulated the gut microbiota of Tg mice (doi.org/10.1038/s41422-019-0216-x0).

    I am surprised to find out that the microbiome data did not support the hypothesis that GV-971 can alleviate inflammation via modulation of the gut microbiota.

    This piece of data is in Fig 4 (attached to this email).

    Fig4a is a Principal coordinate analysis (PCoA) of the gut microbiome composition at the species level (OTUs) based on the Bray-Curtis distance for Tg and GV-971-treated Tg mice. This shows that these two groups of mice are significantly different between their gut microbiota. This could be an effect of GV-971 on shifting the gut microbiota of Tg mice to a different space. This means that GV-971 changed the gut microbiota of Tg mice.

    Fig4b is a Heatmap of significantly changed gut bacteria represented at the genus level between Tg and GV-971-treated Tg mice. Among the taxa that were significantly promoted by GV-971 were those that contains opportunistic pathogens which may aggravate inflammation. Typical example is the family Desulfovibrionaceae. Members of this family when found in human or animal gut are endotoxin and hydrogen sulfide producers which can induce or aggravate inflammation. This means that proinflammatory gut bacteria were promoted by GV-971. Among the taxa that were significantly diminished by GV-971 were those that can produce short chain fatty acids (SCFAs) such as Roseburia spp. Members of Roseburia can produce butyrate that can mitigate inflammation. Increased abundance of this genus has been associated with weight loss and reduced insulin resistance in mice. Astonishingly, this potentially beneficial, anti-inflammatory group of gut bacteria was reduced by GV-971.

    Taken together, the microbiome data provided in the Cell Research paper, being associative in nature, did not support the hypothesis that part of the mechanism for GV-971 to alleviate AD might be reducing inflammation by way of modulating the gut microbiota.

    On the contrary, the microbiome data provided in the Cell Research paper indicate a possibility that GV-971 may aggravate the dysbiosis of the gut microbiota and thus potentially increase inflammation in AD mice.

    It is very unfortunate to see that such conflicting microbiome data against the paper’s hypothesis escaped the scrutiny of both the authors and the reviewers.

  20. Skeptical says:

    Thank you for that, Liping. I’m not a microbiome specialist, but I’m enough of a microbiologist to think you have a point.

    I also need to note that a (presumably) closely related carbohydrate* was claimed to cause the apoptosis of cancer cell in vitro by binding to and inhibiting the polymerization of tubulin (doi:10.4161/cbt.10.1.12167). Pharmacologically, it seems unlikely to me that a sulfated oligosaccharide would get into cells, even in culture. And for similar oligosaccharides to be able to bind amyloid, bind tubulin, kill cancer cells, and beneficially alter the host microbiome is a stretch.

    * “JG3, a novel form of sulfated oligosaccharide isolated from brown alga is structurally characterized as a 1,4-linked β-D-mannurarate of pyranohexuronic acid residues bearing an average of 1.5 sulfates at 2-hydroxyl and partial 3-hydroxyl groups and 6-carboxyl groups per sugar residue, with an additional C1 carboxyl group at the reducing end.”

  21. Tom says:

    Image duplication reported on pubpeer in the original GV-971 paper.
    https://pubpeer.com/publications/610206AC7EC968E85BA8389C674A3C#4

  22. SGM says:

    Yeast-derived mannan oligosaccharides are well-established animal feed additives that apparently cause significant beneficial changes to the microbiome and immune function. It wouldn’t be so surprising if the improvement in gut health were neuroprotective. I hope so. And I also hope that eventually there will be genuine validation while yeast wall parts (or other cheap source) can provide an accessible (low or no IP barrier) therapeutic approach for anyone. This is an interesting article from a supplier of a MOS product. https://pdfs.semanticscholar.org/893b/4ec8355f4338cc139c2e2e4de584c5543a52.pdf

  23. Anonymous says:

    There is a dietary supplement sold OTC and promoted by a former NFL quarterback and his movie star wife that they allege promotes weight loss “without changing your lifestyle or eating habits.” It contains MOSs derived from the konjac root. The scientific evidence of its effectiveness for weight loss is kind of sketchy. The advertised brand claims to have millions of satisfied customers. I wonder if those customers show an AD benefit, even if they don’t lose weight?

    Also, does anyone know the major differences between the seaweed MOS product and the konjac root MOS product?

    DISCLAIMER: I have no financial interest in the endorsed product, I don’t use it, and I believe the studies that say it is not effective.

  24. SGM says:

    GV-971 is quite different from konjac MOS and yeast MOS, so it was a bit of a non sequitur for me to mention the latter I guess. The reason I’m thinking there may be commonalities is that mannose even as a free sugar is apparently special in its ability to inhibit various gut pathogens by binding to surface finger-like projections — see the above pdf. That observation was the origin of the development of the Alltech animal feed product from hydrolyzed yeast. But various biological effects may depend on lots of things, for example, branching-patterns creating different affinities to receptors, amount of free sugar (bad) hydrolyzed in the gut, and physical properties of the substance; if it is an emulsifier it might be a “soap” that washes away protective intestinal linings*.

    [I have a financial interest in the continuing availability and affordability of a yeast probiotic capsule product for humans that I repackage in #4 capsules and shoot down the throats of two 14 yo IBD cats (2 #4 capsules bid each = 4 each per day). The capsules combine dried S boulardii with the aforementioned Alltech Bio-MOS. It’s not a controlled trial of course and I don’t know whether its the MOS or the dried yeast that are more important for the effects, but as long as I keep up the capsules the previously constipated-and-vomiting cat and the previously diarrhea-all-over-the-house cat are doing very well, and they’ve got their personalities back since I’ve been able to wean them off prednisolone. http://www.rawfeedingforibdcats.org/s-boulardii—review-of-the-science.html%5D

    * https://scholar.google.com/scholar?hl=en&as_sdt=0%2C22&as_vis=1&q=diet*+emulsif*+dysbiosis&btnG=

Leave a Reply

Your email address will not be published. Required fields are marked *

Time limit is exhausted. Please reload CAPTCHA.