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Dr Naviaux's Suramin & Autism Trial - publication and interview

Discussion in 'Other Health News and Research' started by natasa778, May 26, 2017.

  1. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    From experience I know that once blinding is broken by a systematic tell tale reaction you might as well assume it is defunct. The patients and investigators will know who had the drug.Once that is the case subjective bias ALWAYS rolls in. You would need to be superhuman to avoid it. I certainly could not.

    So the examiner rated scales are unreliable too.
     
  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yup. That is the bit that made me say what I did. Being able to say sentences relies, almost certainly, on other bits of brain. These might improve function secondarily over time but one would expect it to take a considerable amount of time.
     
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  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    From Wikipedia it looks as if side effects on the skin are very common with sermon so ethically the parents would have had to be informed that skin reactions were a significant likelihood. It seems to me likely that the parents of the children who got the drug would have known they had got it pretty much straight away. The parents of the controls would be left wondering.

    I am afraid the way the parents' remarks are reported does not increase my confidence that they mean anything. As indicated in above posts, the biology does not seem to fit very well.


    I'm still reading the paper but just on the pharmocokinetic analysis:


    Yes, but the comment about the data fitting a two compartment model almost certainly takes the mean at each point. I think it must do in fact because if you include all individual values they cannot completely fit any model. My problem is that the researchers seem to be unaware that the fact that their three time points fit a two compartment model indicated nothing except that they fitted a model to the points. Those are the sorts of things that I have learned to look out for when gauging the quality of studies.
     
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  4. Basilico

    Basilico Florida

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    I don't think this is accurate.

    With few exceptions, toxicity often has to do with the dosage than with the substance itself.

    For example, extremely high levels of insulin could be considered toxic because it could cause death. Yet, insulin is critical for survival. Extremely high doses of radiation causes cancer and death, yet we are all exposed to low levels of radiation all the time, and our bodies have developed ways to cope with this. Bananas have low levels of radioactivity, but I've never heard a scientist warning the public that bananas are toxic. Even water in extremely high amounts is toxic, but again it is critical to survival.

    The interview states that Naviaux used an extremely low one time dosage precisely because he wanted to be extremely cautious.

    And while a larger sample would be necessary (as he himself stated) to determine whether there are any uncommon reponses, I think it is significant that besides a minor rash that went away after 2-4 days WITHOUT treatment, there were no other side effects reported. From my understanding, children with autism tend to be extremely sensitive to foods, chemicals, medications, sensory input, etc... so the fact that these 5 kids had such minor side effects seems to support that in such a low dosage, this drug likely did not have toxic effects on them.



    Here are 2 quotes from the interview supporting this:

    Even though suramin has been around for 100 years, it has never been tested in a pediatric autism population before, so this was really uncharted territory. The rationale for the single dose was to err on the side of caution because high doses of suramin given for prolonged periods of time in cancer patients have been associated with significant side-effects.

    It's important to remember though that we were using a very low dose of suramin -- lower than anything that has been tested for any disease in the nearly 100 years that suramin has been used in medicine. To put this in perspective. The low-dose that we used produced blood levels of 5-15 µM. All previous uses of suramin have been at medium doses for African sleeping sickness that produced blood levels of 50-100 µM for 1-3 months, or high doses for cancer chemotherapy that produced blood levels of 150-270 µM for 3-6 months."




    From what Niviaux says in the interview, there were strong side effects from Suranim when adults with cancer and African sleeping sickness were given a much higher repeated dosage for months. These children were given a one-time dosage and their blood levels of Sumarin were 1/10 of what the adults had.




    Additionally, Suramin has been used in humans for 100 years and is on the World Health Organization's list of most important drugs. The reason he chose this drug is that it is the only drug approved for use in humans that would accomplish what he thought needed to be done. I don't understand why you say that he used it because of a mouse study.



    Here is a quote explaining why he used Suramin:

    In 2008, I searched the world for any drug that could inhibit eATP signaling. There was only one drug in the world that was known to do this and was available for use in humans. This was suramin. Suramin has many actions. One of its best-studied actions is as an inhibitor of purinergic signaling. For simplicity, we call suramin an “antipurinergic" drug because it inhibits signaling. There are many other antipurinergics under investigation for other conditions, but most are all still experimental. Suramin had the benefit of being a 100-year old drug that could be tested in humans.
     
    Last edited: May 29, 2017
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  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yes, it is a problem.

    The difficulty with treatment trials is that it is ever so easy to get a 'positive result'. What is much less usual is for all the details of the result to line up in ways that fit with the theory that made you do the trial. The standard detail is a dose response curve but any detail one can think of will do as a cross check. So you may see a face that looks like the Queen. That may be a chance finding. However, if she is standing on the balcony at Buckingham Palace that helps. If she has a tall chap looking like the Duke of Edinburgh beside her that helps. If she is wearing a matching pastel suit and hat that helps. But if she is wearing dungarees you wonder.

    That may sound 'unscientific' but I think everyone will agree it is pretty reliable - because we have stores of relevant knowledge much of which we are unaware we have. In science that relevant knowledge is a very powerful way of checking whether results are what they seem to be - just like the face like the Queen.

    A gut-brain connection does not help. It remains implausible that language centres would suddenly upgrade their function in a consistent way because of some generic chemical signal from elsewhere with in brain or gut.
     
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  6. Jesse2233

    Jesse2233 Senior Member

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    @Jonathan Edwards do you think it's possible that systemic metabolic improvement caused by suramin could lead to improved brain functioning? and what do you make of the normalized metabolites in Figure 4?
     
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  7. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Skeptical about this.. Loved to be proven wrong
     
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    A systemic metabolic improvement can lead to improved brain functioning - we know that from other conditions like hypothyroidism. But it is usually slow. I find the reporting of metabolites confusing - for reasons I gave before. I would be able to follow it they had picked five metabolites they expected to improve and a few controls. Once you have omics it is all very obscure to me.
     
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  9. Jesse2233

    Jesse2233 Senior Member

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    Might it be faster and more profound if an inhibiting signaling switch is suddenly blocked and the (presumably) undamaged mitochondria resume normal functioning?
     
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  10. alex3619

    alex3619 Senior Member

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    A case in point, even oxygen can be toxic in too high a dose. Toxicity findings are often part of what is used to determine maximum safe dosage, though the safe dose varies from person to person due to pharmacokinetics issues (enzymes, cofactors, age etc.) so that a maximum safe dose may still be toxic for a small percentage of patients.
     
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  11. alex3619

    alex3619 Senior Member

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    Which is why I keep talking about objective outcome measures. A dose response curve is one of those.
     
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  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I doubt it. Rapid improvement might occur if it was restoration of a previously normal intellectual function but in Autism the normal function has not yet developed. Giving thyroxine to adults with recent onset severe hypothyroidism can produce quite rapid benefit in wakefulness and thinking but when given to congenitally deficient infants catching up development is slow. Moreover, if there were actually a mitochondrial function defect in brain areas like language centres sermon would not reach those so would be unlikely to have an effect.
     
  13. Jesse2233

    Jesse2233 Senior Member

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    Thank you professor. Perhaps I'm grasping at straws, but what if the intellectual function was developed but unable to be expressed given metabolic disruptions (that subsequently get ameliorated off by blocking the purinergic signal).
     
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  14. dannybex

    dannybex Senior Member

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    Not sure if this has mentioned, but I'm not so sure that's always the case. With of course exceptions, drug companies are often looking for 'treatments', or drugs that temporarily 'manage' or suppress symptoms, instead of things that actually address the cause or causes of illness.

    Anyway, it looks like suramin has indeed been studied for a variety of cancers:

    https://www.ncbi.nlm.nih.gov/pubmed/2926472

    https://www.ncbi.nlm.nih.gov/pubmed/2285603

    https://www.ncbi.nlm.nih.gov/pubmed/8637045

    This one mentions 'serious toxicity'...

    https://www.ncbi.nlm.nih.gov/pubmed/7955436
     
  15. BurnA

    BurnA Senior Member

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    Just FYI, Ron Davis made a point of talking about suramin side effects at iimec12, he said we shouldn't be comparing to cancer doses as they are often increased to the level of tolerability of the patient.

    Giving the autism trial as an example, if the worst side effect turns out to be a rash how bad is that.
     
  16. RogerBlack

    RogerBlack Senior Member

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    To be fair, hunting for the root cause of a disease adds often a step which may significantly delay drug development, over treating symptoms.
    For example, there has been considerable research into ways to eliminate HIV from the body, and over a billion dollars spent, with no concrete results yet.
    Similarly with arthritis - nobodies nailed down a precise mechanism and druggable target, though I gather from a quick look that possibly less has been spent doing this than for HIV in recent years.

    Adding a billion dollars or three and a few years into finding the root cause of a condition, when finding that root cause may not in fact lead to a ready treatment is something drug companies pretty much can't do, if there is an accessible druggable path that interrupts the symptoms.
     
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  17. pattismith

    pattismith Senior Member

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    I read that Suramin was tested on HIV patients with no success. It happened that some of them were HIV and had also cancer, and that even though the effect on HIV was zero, the cancer were cured...
    This result lead to more studies on Suramin to treat cancer.
    There was also a study that showed improvment on Mice Atopic Dermatitis, which means that Suramin has also anti inflammatory properties.
     
  18. Jesse2233

    Jesse2233 Senior Member

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    This is a somewhat disturbing account of an adult autistic patient treated with Suramin by a doctor out of a trial setting. Setting aside the unfortunate context, the results seemed positive:

    From Reddit:
    Unfortunately I can't seem to find the documents he or she is referring to
     
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  19. Manganus

    Manganus Senior Member

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    This is particularly important to remember.
    We are not served by dismissing research due to unwanted results.
     
  20. Manganus

    Manganus Senior Member

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    It seems as if you know a lot more than you write here. ;)

    The "toxicity" you're referring to, is that gastritis (etc.) ???
     

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