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

natasa778

Senior Member
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1,774
The second mother made a big deal out of one sentence her son made, and maybe it was a bit deal, but it sounded fairly minor to me and open to interpretation.

But this is coming from a zero knowledge of autism, maybe it was a very big deal.


It is an absolutely mega MASSIVE deal. The equivalent of an ME patient who has been bed-bound for 12 years getting up and going for a light jog around the block.

Not a kind of thing that could ever happen through someone else's wishful thinking.
 

Jesse2233

Senior Member
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1,942
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Southern California
From one parent. I'm sure many can relate to trying every new treatment for a decade to have find nothing that works
"We have tried every new treatment out there for over 10 years. Nothing has come close to all the changes in language and social interaction and new interests that we saw after suramin,” the parent of a 14-year-old boy in the study said in a statement. “We saw our son advance almost three years in development in just six weeks."
 
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It is an absolutely mega MASSIVE deal. The equivalent of an ME patient who has been bed-bound for 12 years getting up and going for a light jog around the block.

For me an ME patient who has been bed bound who gets up and goes for a jog, is recovered in my book.

For a kid to go from saying "I did it" to I'm done with dinner" is progress, but I would have been a lot more convinced if the mother gave other examples of sentences.

I hope it works out.
 

natasa778

Senior Member
Messages
1,774
For me an ME patient who has been bed bound who gets up and goes for a jog, is recovered in my book.

For a kid to go from saying "I did it" to I'm done with dinner" is progress, but I would have been a lot more convinced if the mother gave other examples of sentences.

I hope it works out.

That imaginary bed-bound ME patient did go for a jog that one day, but the effects were not long-lasting. These parents' reports remind me of rituximab reports, where most responders slide back to baseline after a while. Does that mean that rituximab effects were not real?

Fluge&Mella started their research on the basis of one patient's subjective report of improvements. Imagine for a sec ... if they'd employed that same dismissive philosophy of "subjective-reports-of-improvement-don't-mean-a-thing", and improvements seen in "only" 5 patients, no matter how massive they were, don't mean others would benefit = rituximab not worth pursuing as a treatment for ME.


Many people, including many parents, are absolutely terrified of a paradigm change in autism, for various deep and very personal reasons.

(Think how hard ME-paradigm change is and multiply the resistance factor by 1,000)
 
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hixxy

Senior Member
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1,229
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Australia
But the drug dose not cross the blood brain barrier and the bits of the brain responsible for language are pretty guaranteed to be behind the blood brain barrier.

Is this really a problem? If suramin continues to work in a larger trial I think this just tells us even more about the disorder ie that the pathology that is perpetuating the "cell danger response" is not in the brain and that the effects on the brain are "collateral damage". One explanation could be the gut-brain connection.
 

barbc56

Senior Member
Messages
3,657
@hixxy

If Autism is neurological, it absolutely makes a difference. I believe most of the medical world believe it is. But the devil may be in the details.

While this is interesting, it's important to keep in mind that when studies with small numbers the odds Increase that larger studies don't necessarily show the same results.

Intriguing, though I would take the parent reports with a grain of salt. It's understandable that hope might change a parent's perception as there's a possibility they become hypervigilant about any sign of change.

But time will tell.
 
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10,157
Unless you have something specific that you base this opinion on, this opinion says more about yourself than it says about Naviaux and his research.

It really just reads like plain old pessimism to me.

It's not just 'plain old pessimism'. I have quite a few reasons why I said what I did. Possibly too many to lay out here and maybe not even coherently due my own brain limitations right now.

I have been trying all day to post my reasons. I can't do it.

In a nutshell:

I have a problem with his previous mouse study which was focused on both autism and schizophrenia.

Looking into APT (Anti-Purinergic Therapy) and Naviaux's Cell Danger Response theory it is really hard to find anything written by anyone other than Naviaux. I could be wrong about that, I just seem to be finding theory rather than actual research to demonstrate its existence and relationship to neurological dysfunction.

I have a problem that his theory/research is at odds with a lot of the current research. You can't really apply his theory or research to a lot of the research that exists presently. I am fully aware that he says you can. I don't agree.

I am prepared to say that if Suramin does prove to be effective, it would only work in the subset of people with autism who have a particular defect in the purinergic pathway. Research has clearly indicated multiple causes. I wonder how Naviaux was able to choose children with this particular defect. I do not believe that all children with autism have this defect as the research indicates otherwise.

I have a problem with his mouse-model of autism. Fear of strangers, poor coordination, fear of novel situations is not limited to autism. And where on earth does Schizophrenia come into the research as it is more of a problem related to dopamine.

As for the present study, I have a problem that N=5 is being heralded as some how meaningful or significant especially when the results were confounded by the rash that appeared in the children given Suramin.

I have a problem that children were given a dose of a toxic drug based on a mouse study.

Even Naviaux said that Suramin can't be used for more than a few months without a risk of toxicity in humans. So why expose children to it all -- why not work on developing a new similar drug with less side-effects without exposing children to a toxic drug. That would be worth a ton but then again not if it doesn't work.

If what Kent Heckenlively said is true that Naviaux told him that if suramin works out autism will end, well all I can say is that is a huge red flag.

I have a problem with the fact that the medication does not distribute well into CSF, doesn't cross the blood brain barrier, that it is not extensively metabolized, and about 80 percent is eliminated by the kidneys. How can a medication have such dramatic neurological effects if it can't even get to the parts of the brain it is supposed to have an effect and only a small amount gets metabolized at all.

As J. Edwards says the details dating back to the mouse study are not lining up well. Naviaux seems to have a lot of answers to some of the questions about the study and they don't seem to be backed up with any kind of scientific proof.

That might seem too quick a conclusion so maybe we should consider some of the detail. The signature of good science is that the detail lines up well. We have reports here that children said their first sentence within a day or so of getting the drug. But the drug dose not cross the blood brain barrier and the bits of the brain responsible for language are pretty guaranteed to be behind the blood brain barrier. So it looks as if the parents' reports were maybe flavoured by optimism. That does not help either

More about Suramin at the following link:

http://www.sciencedirect.com/topics/page/Suramin

So excuse my pessimism, if that's what you want to call it. It doesn't add up for me from what I know about autism and my own experiences with my daughter and other autistic children. I don't think much will come of this.

The way that his research has been presented by the press is giving false hope. And would think that some pessimism is justified. Let's see what comes next -- further support, more positive results and more supportive research re: his CDr theory ... . There are many questions to be answered. To prematurely state this is the answer -- well how many times do studies like this not go any further, or can't be replicated ... .

All of this is my opinion, if I am totally wrong, I will gladly discuss when there is more supportive research.
 

alex3619

Senior Member
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Logan, Queensland, Australia
Most small pilot studies go nowhere. A pilot study is to demonstrate potential, not prove anything. What it does do is show there may be something there, and given the size of the potential payoff its worth pursuing.

Now when an effect size is really large, and its hard to judge how big the effects were in subjective reports, then even a pilot study can be very valuable.

The issue is not whether or not this is proven to be a good treatment. It has not. The issue is to whether such a treatment could be allowed to not progress to more in depth studies. Like I said with XMRV, there is enough evidence to warrant further investigation. Given the cost of even a small study this might be an issue though. Where is the funding coming from?

When we have a larger study done, and if they focus on key metabolites (to decrease costs) and objective outcome measures (what is it that can be measured I wonder?) then this could wind up something very interesting.

Let us also not forget that this drug is really really old. There might be big issues to getting it approved however, due to no pharma backing and the lack of modern safety studies. Rituximab or even cyclophoshamide might be approved much faster. In its favour though, this being an old drug means there is a century worth of information on it. It might be that it can be fast tracked provided there is will in government, FDA etc.

PS If this drug can be shown to work then perhaps other drugs with similar targets and that are officially approved already might also be tested.
 

BruceInOz

Senior Member
Messages
172
Location
Tasmania
Looking into APT (Anti-Purinergic Therapy) and Naviaux's Cell Danger Response theory it is really hard to find anything written by anyone other than Naviaux. I could be wrong about that, I just seem to be finding theory rather than actual research to demonstrate its existence and relationship to neurological dysfunction.
This certainly bothered me when I read Naviaux's metabolomics paper when it first came out a while ago. Not just that I could find no references to the Cell Danger Response other than those authored by Naviaux, but that he spoke about it as if it were well established.

Of course, science needs maverick thinkers and Naviaux should be encouraged and supported to take his ideas as far as he can. Science history is full of out-of-the-box thinking that went against the established ideas and were proven correct (e.g., Barry Marshal, Helicobacter pylori and stomach ulcers). But for every maverick that was proven correct, there were many more who were proven wrong and their ideas are now forgotten. We don't yet know which side of history Naviaux's Cell Danger Response will be on and it will probably be some time before we do.

In the meantime, I see a little of @Kina 's pessimism as protective. Pinning all your hopes on another theory that doesn't pan out can become emotionally draining. I'm not dissing those who are optimistic about where this may lead; just pointing out there is nothing wrong with a dose of realism and even pessimism also.
 
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I'm not sure if it will be an answer—I read the comment about rituximab, and I've never been able to figure out what percentage of people stayed recovered, what 'recovery' actually was, and even when pointed in the right directions, still can't get a fix on that. Yet, I know clinics are suggesting people try it.

That said, Naviaux seems to be taken quite seriously by many of the quite-serious researchers into ME/CFS. If his ideas and claims can be easily batted aside (as it seems to be many times in this thread), I'd think that wouldn't be the case.
 

Solstice

Senior Member
Messages
641
This certainly bothered me when I read Naviaux's metabolomics paper when it first came out a while ago. Not just that I could find no references to the Cell Danger Response other than those authored by Naviaux, but that he spoke about it as if it were well established.

Of course, science needs maverick thinkers and Naviaux should be encouraged and supported to take his ideas as far as he can. Science history is full of out-of-the-box thinking that went against the established ideas and were proven correct (e.g., Barry Marshal, Helicobacter pylori and stomach ulcers). But for every maverick that was proven correct, there were many more who were proven wrong and their ideas are now forgotten. We don't yet know which side of history Naviaux's Cell Danger Response will be on and it will probably be some time before we do.

In the meantime, I see a little of @Kina 's pessimism as protective. Pinning all your hopes on another theory that doesn't pan out can become emotionally draining. I'm not dissing those who are optimistic about where this may lead; just pointing out there is nothing wrong with a dose of realism and even pessimism also.

Well, case in point for me. My excitedness is now dampened but that isn't a bad thing. What I, and I guess we, want more than anything is good science and that can't go without challenging everything imo. As that, input like from @Kina and @Jonathan Edwards is invaluable to me, aswell as several other good comments. I'd hate for us to go down the path the BPS lot went, where science can't be critiqued.
 

Countrygirl

Senior Member
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UK
http://www.economist.com/news/scien...-initial-trial-suramins-effects-were-dramatic
20170603_blp904.jpg


MICE are not humans. But they are close enough that many drugs that work in mice turn out to work in people, too. Three years ago Robert Naviaux, a researcher at the University of California, San Diego, published a paper suggesting that a drug called suramin could alleviate the symptoms of autism in mice. That was interesting, for despite all the research into autism, few effective treatments are available. Now things have got more interesting still. In a paper just published in Annals of Clinical and Translational Neurology, Dr Naviaux has repeated his experiments on humans, and found that the drug seems effective for them, too.

Nobody is sure what causes autism. But one theory is that it stems from a phenomenon known as the "cellular danger response". This involves compounds circulating in the blood, known as purines, which command cells to halt their normal activities and brace for an imminent viral attack. That response is normal and, provided it switches off when the danger has passed, beneficial. But some researchers believe that the mechanism can end up switched on permanently. This, they think, can encourage the development of autism.


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Nor is this simply conjecture. Dr Naviaux’s past work with mice shows that when mothers are exposed to a virus-like stress while pregnant, the cellular danger responses of their pups can become permanently activated. And one side-effect of the response is to inhibit the growth of neural connections that is normal in young brains. The result is a set of behaviours - difficulty with social situations, and a strong preference for familiar things and for routine - that bear a strong resemblance to autism in humans.
 

alex3619

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Logan, Queensland, Australia
we, want more than anything is good science and that can't go without challenging everything
Pretty well. Challenges mean the researchers have to use tight research methods, and get to rethink the weak points in what they have done. Challenges can dampen enthusiasm for the hypothesis, kill the hypothesis in its current form, or lead to even better science.

What can happen is a clash between advocacy and science. The roles are not the same. We need to advocate for our researchers, though also expect good science. From a scientific perspective its criticism that makes for good science. The two roles are not fully compatible.

My hope is that a follow up study will take these criticisms and provisos etc. into account, and produce the kind of research that will quickly advance into even more studies or finally put it to rest due to insufficient evidence. Either result is a good one, though I would prefer to see success as so many have been waiting for so long for treatments.
 

heapsreal

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@heapsreal It seems unlikely it has anything to do with antiretroviral activity given that it had (mostly) the same effect in their mouse model of autism and very much doubt the mice were infected with a retrovirus by coincidence.

Until they know with 100% what causes autism, then any cause is possible. There are many researchers that think autism has links with some type of infection, not just a RV but even just a normal virus. Retroviral drugs do have effects against other infections not just retroviruses eg some arvs are used for hepatitis. Im just keeping all options open until theres a definitive answer.
 

Countrygirl

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http://cfspatientadvocate.blogspot.co.uk/2017/05/robert-naviaux-autism-and-mecfs.html

SATURDAY, MAY 27, 2017
this and this. A year later there was this intriguing study and also this similar study. Dr. Naviaux proposed early on that a 100 year old drug named Suramin might have some activity against the "cell danger response" in Autism.

Today came a new study that moved this treatment to a small group of young boys. The study was published in Annals of Clinical and Translational Neurology. The purpose of the trial was to test the underlying theory about a cause for autism and to assess the safety of Suramin. The results were quite striking, but right on target for Dr. Naviaux's supposition regarding Suramin. There is an article about this new study here. Also there is a youtube video of Dr. Naviaux speaking of this study and its participants. Additionally Dr. Naviaux answers questions on today's study here.

Dr. Naviaux has provoked a shift in the underlying cause of Autism - towards a metabolomic signaling breakdown. This is a seismic shift. Time will tell us how real this is.

ME/CFS
There is some thought that the purinergic signaling in ME/CFS is also aberrant. I first heard of this in a presentation by Dr. Geoffrey Burnstock at a 2011 Invest in ME conference in the UK. Next week the 12th Invest in ME conference will be held in London. Invest in ME does an excellent job at promoting serious ME research. Perhaps Dr. Naviaux will attend this conference? There he could meet Donald Staines and talk about Vasoactive Intestinal Peptides and other neuro-peptides. In this business of ME/CFS, there is never any assurance that the right people are talking together.

More recently, Dr. Naviaux has focused on ME/CFS. He has communicated with various CFS physicians and researchers, including Dr. Paul Cheney. Dr. Cheney has long promoted the notion of ME/CFS being a "Dauer state" or a self-protecting down-regulation. Dr. Cheney's protocol leans towards correcting a hampered metabolism in his patients.

Dr Naviaux and his research is connected to the Open Medicine Foundation. He works closely, as well, with Dr. Ron Davis at Stanford and Dr. Eric Gordon at Gordon Associates.

The post below reviews Dr. Naviaux's important study on ME/CFS patients in 2016. Yesterday, Dr. Naviaux did a follow-up webinar sponsored by the CDC. The slides can be found here. This presentation includes this: "hallmarks of a low energy state: anxiety, restlessness, irritability, fear of change, OCD behaviors, sensory and chemical hypersensitivities, meltdowns, and bouts of hyperactivity and even seizures." Sounds familiar.

It is worth noting that Suramin has various actions.This fact intersects nicely with some past, supposedly failed, research in ME/CFS.

All this is pretty amazing stuff. Dr. Naviaux's ideas seem to be reshuffling a number of hypotheses about these serious ailments.

As with all research, the biggest obstacle to moving forward is money. I have followed type 1 diabetes research for 25 years. It is a tough road for innovative researchers to get enough money to actually do the work, especially if the researcher is seen as an outsider - and when there are unseen or undeclared forces standing in the way.

Fifteen years into my daughter's illness, her caregivers and I struggle to make her better. Hope is not the answer. Research and treatment are. Dr. Naviaux's work is most welcome. All those connected to the illness need a little practical results and direction in order to gain some traction.

Meanwhile, patients and advocates are left to struggle on their own. All, according to their abilities and finances, try to find a way out of this disease. In my limited experience, different things work for different people - and some enterprising or lucky individuals can actually get better.

****It is worth noting that there has existed for some years now a comprehensive urinary metabolites test that measures 70 different metabolites. This organic acids test is available from Great Plains Laboratory and other labs. I see the OAT as a crude precursor of Dr. Naviaux's metabolic studies. However, it is an existing instrument with actionable information. The patient, advocate or even a doctor can learn to read this test and make decisions.
 

alex3619

Senior Member
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Logan, Queensland, Australia
keeping all options open until theres a definitive answer.
... or as I put it, when you don't know where something is, you look everywhere.

PS It does not even have to be an infectious or active retrovirus, the issue here might well be how we are responding, not what a virus is doing. Currently we have issues finding any known pathogen as a primary cause. We can however find viruses, but not acute viral infection. With retroviruses the key thing for most is the presence of reverse transcriptase. I am still amazed there has not been a modern study looking for this, even to just rule it out. Past studies have found it, but not reliably. Similarly there are subgroups with specific pathogenic infection, and then there is HHV6 which does not need reverse transcriptase to rewrite our genetic code.
 
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RogerBlack

Senior Member
Messages
902
Even Naviaux said that Suramin can't be used for more than a few months without a risk of toxicity in humans. So why expose children to it all -- why not work on developing a new similar drug with less side-effects without exposing children to a toxic drug. That would be worth a ton but then again not if it doesn't work.

Because developing a new drug would take a large slice of a hundred million dollars, and can't be done without a decent idea if suramin actually does anything, and what it does.

You might try to design a drug without the 'toxic' bits - and spend a long time working to prove its safe, at which time you find that it's the response to the toxic effects which is actually doing it, and you need to work on selectively applying the toxic effects to provoke an immune response in some tissues.
(mechanism entirely exemplary - I have no reason to believe it's this)