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

hixxy

Senior Member
Messages
1,229
Location
Australia
Does anyone know if there was confirmation in any of the interviews or articles that Naviaux plans to do a pilot trial of suramin in ME/CFS patients? Or is it just still a rumour?
 

bspg

Plant Queen
Messages
547
Location
USA
Does anyone know if there was confirmation in any of the interviews or articles that Naviaux plans to do a pilot trial of suramin in ME/CFS patients? Or is it just still a rumour?

From Dr. Naviaux's phone presentation with the CDC on 5/25/17:
"Pilot study of low-dose suramin in CFS is seeking funding to launch later this year."
They do need more funding for it. Donations can be made here: http://naviauxlab.ucsd.edu/support/
 

TiredSam

The wise nematode hibernates
Messages
2,677
Location
Germany
I think there's a distinction to be made between the study itself and the ridiculous write-up it got from Kent Heckenlively:

http://bolenreport.com/study-will-end-autism/

The Study Which Will END Autism!
And probably Chronic Fatigue Syndrome ME/CFS as well…

I always tell my students that when a scientific concept is finally understood the answer should be simple, elegant, and yes, even beautiful in its own way. That moment has NOW been reached in autism and the results published for the entire world to see.

I know there are FACTIONS in the autism community, as well as in the chronic fatigue syndrome (ME/CFS) community. But it is time to put those differences aside and unite to support this research. The FATE OF ALL OF US depends on joining together in common cause to end these epidemics.

By Kent Heckenlively, JD

The above article reads like something written by a bit of a nutter with an agenda. But I don't see why that should reflect poorly on Naviaux or his study. Just ignore the article and judge the study on its own merits.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I just hope he's right. At this point, we don't know, but his work is a great start.
BY the way, I attended a science webinar talking about metabolomics. The attendees were in the thousands, from all around the world. And the CEO of Metabolon made a mention of how much of a breakthrough metabolomics profiling was a game changer for ME. The tide is turning.

My immediate reaction is the same as Kina's, but I would like to unpick that a bit.

When I did my first trial of rituximab in RA it was just 5 patients and the paper was turned down by the editor of our mainstream journal on those grounds. But I pointed out to him (in his office) that the probability of getting over a hundred objective data points all fitting in nice neat pharmacodynamic curves by coincidence was pretty much zero. So he agreed to publish. So maybe Kina was oversimplifying.

But that was a very unusual situation. In the vast majority of cases Kina is right. Five cases is unlikely to tell us anything. If we then look at the detail the worries immediately appear. The outcome measure is subjective. All the treated patients had a rash of the same sort so the study was unblinded. That pretty much writes off any useful interpretation.

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.

Then we are given a pharmacokinetic analysis with three data points on log plots. We are told that these data point fit 100% into the pharmacokinetic model. Trouble is that with a two compartment model any set of three data points fits 100% by definition. I may have misread here but again I am concerned.

We then have the complicated metabolomic analysis. The problem here is that however useful metabolomics might be for mechanism discovery it is the wrong method in this situation because the data are statistically useless. For a small study like this the right thing to do is to measure 5-10 things at most having decided in advance which way you think they should change if your hypothesis is right.

I am not surprised that thousands of people go to metabolomics meetings. That is true for trendy subjects. For cutting edge subjects there is usually about twenty people. Metabolomics is great for trying to find an answer when you have no idea what you are looking for but it becomes irrelevant once you have a clear hypothesis. You know what you need to measure. You can measure some other things as controls but that is not metabolomics.

Another point we have discussed before is that animal models are pretty useless for identifying causal mechanisms. There are usually about 100 ways of inducing an animal to show signs similar to disease X. That means that for any one model there is a 99% chance that it does not reflect the cause of disease X.

One can always be wrong, and I have been wrong a few times but for me this study does not hang together.
 

A.B.

Senior Member
Messages
3,780
But that was a very unusual situation. In the vast majority of cases Kina is right. Five cases is unlikely to tell us anything. If we then look at the detail the worries immediately appear. The outcome measure is subjective. All the treated patients had a rash of the same sort so the study was unblinded. That pretty much writes off any useful interpretation.

I think you're being too pessimistic about the blinding.

Another potential limitation of the trial was the self-limited rash. The rash was asymptomatic and resolved spontaneously in a few days. In theory, the rash may have biased parents in a way that caused them to either improve their scores on the ABC, ATEC, RBQ, and CGI, or to report more side-effects or adverse behaviors at both the 7-day and 6-week reports. Examiner-based ADOS scoring was more resistant to this potential bias, since the rash was not visible on exposed skin to the outcome examiners at any time. However, a design limitation of the study was that one of the two ADOS examiners was also assigned to conduct scripted phone interviews with the families, and might have been susceptible to unconscious bias even though the study remained blinded and the rash preceded any significant examiner-based outcomes by one and a half months.

The examiner rated ADOS scores improved significantly.
 

A.B.

Senior Member
Messages
3,780
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.

Did you read this part?

Previous studies have shown that suramin is taken up into the CNS at the level of the brainstem, although not appreciably into the cerebrum or cerebellum.[13] There are eight circumventricular organs (CVOs) in the brain that contain neurons that lack a blood–brain barrier.[49] The area postrema in the brainstem is one of these CVOs that monitors the chemistry of the blood and transduces this information to higher centers in the brain for neuroendocrine, affective, cognitive, and behavioral integration.
 

Hutan

Senior Member
Messages
1,099
Location
New Zealand
@Jonathan Edwards, yes the unblinding due to the rash is a problem. The parents' testimonies are quite compelling though. I wonder if the parents of the boys with the placebo knew what treatment their boys had been given.

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

Then we are given a pharmacokinetic analysis with three data points on log plots. We are told that these data point fit 100% into the pharmacokinetic model. Trouble is that with a two compartment model any set of three data points fits 100% by definition. I may have misread here but again I am concerned.

Actually there are five data points for each of the three measurement times. At each measurement time, the plasma concentration was very similar for each of the five boys. I don't see anything there to be concerned about. Yes, five patients is a low number but this preliminary pharmacokinetic analysis is not a reason to doubt the whole study or the researchers.

Of course, all the pharmacokinetic analysis tells us is that there was suramin present in the plasma and both the initial levels and decline in levels over time was fairly consistent for all five boys. It doesn't tell us if the suramin had a beneficial effect.
 

shannah

Senior Member
Messages
1,429

natasa778

Senior Member
Messages
1,774
Did you read this part?

Previous studies have shown that suramin is taken up into the CNS at the level of the brainstem, although not appreciably into the cerebrum or cerebellum.[13] There are eight circumventricular organs (CVOs) in the brain that contain neurons that lack a blood–brain barrier.[49] The area postrema in the brainstem is one of these CVOs that monitors the chemistry of the blood and transduces this information to higher centers in the brain for neuroendocrine, affective, cognitive, and behavioral integration.

Thank you. This is a hugely important point.
 
Messages
2,087
I may have missed seeing it but it doesn't appear that this video clip with Dr. Naviaux has been posted yet.
That was interesting.
The first mother said she knew straightaway her son got the drug because of the rash, although she also said his speech did not improve.
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.
 

Aroa

Senior Member
Messages
109
Location
Spain
@Kina I know it is difficult for us to understand how you may feel as a mother and of course I don´t know anything about Autism

But It is impossible to develop a study with more patients without funding.

I think Dr. Naviaux thoughts should be taken into consideration seriously. He already has an impressive curriculum.

As a science illiterate , I think his metabolomics study meant a change in the way Me was looked at. He showed it was a hypometabolic disease with a specific metabolic signature. And probably it gave some clues for some specific things to be studied in further detail.

Please don´t lose the hope. All the best :heart:
 

Orla

Senior Member
Messages
708
Location
Ireland
That was interesting.
The first mother said she knew straightaway her son got the drug because of the rash, although she also said his speech did not improve.
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 would be a very big deal. It is even a big deal in milestones once a healthy child moves from using single words to stringing a few words together, and then eventually starts speaking in full sentences. I can well imagine this would mean so much more to a parent of a child with severe autism who had not been developing verbally at the same rate of their peers.

But at the end of the day this was a very small pilot study, so we'd need more research. Some of the articles on it are click-bait but it doesn't mean there are no interesting findings in the study.

I hope they use some objective outcomes for the ME study, as blinding looks like it will be a problem due to side effects. I'd like some subjective findings to be looked at also, and tracking of side-effect severity. I know it will just be a pilot study so not sure how much of this they can fit in.
 
Messages
5,238
Location
Sofa, UK
The abstract says there were two primary outcomes: ADOS-2, which seems to be a subjective assessment, and Expressive One-Word Picture Vocabulary Test (EOWPVT), which sounds somewhat more objective. On EOWPVT, the results say the scores did not change. Further grounds for scepticism that the treatment really was effective, perhaps?

This would be exciting if it pans out, but from such a small pilot with equivocal results, all one can say is that it might be worthy of further study. However exciting the parents' subjective reports are, I think 'cautiously optimistic' would be going a bit too far based on this evidence. Like everyone, I'd love this to be a breakthrough, but I think we have to wait for bigger and better results before there's real grounds for cautious optimism.
 

Murph

:)
Messages
1,799
If your priors are set against suramin working, then obviously this study should lead you to continue to remain skeptical. It is not trying to change your mind, yet.

The paper's conclusion says that "the generalisability of the findings is unknown." Obviously a sample of ten and a treatment group of five is a pilot study. The paper says: "This was a pilot study designed to obtain activity data and effect size estimates upon which future sample size calculations could be based."

This study did turn up some interesting things that will inform future studies.

One thing Naviaux learned is that 45 days was too long to wait to get the official clinician analysis of improvements. The best results were obtained earlier, via the parent surveys taken during the study. (Parents were telehponed daily then weekly.)

Here are some of the charts that depict differences between saline and suramin. You can see the differences are especially strong at the seven day mark. Despite the small sample size they are statistically significant because the effect is reasonably large and reasonably consistent in the treatment group, and not in the other group.

For anyone whose knowledge of Naviaux and/or of the animal model studies led them to set their prior beliefs to allow some chance suramin could really help, these charts will potentially cause you to update your beliefs.
Screen Shot 2017-05-28 at 9.49.01 PM.png
Screen Shot 2017-05-28 at 9.49.12 PM.png
 
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Demepivo

Dolores Abernathy
Messages
411
Dr Naviaux has been in discussions with the OMF about funding an ME/CFS Suramin study.

Hopefully this can be sorted out soon.

He has been inundated with inquiries over the last few days about the CDC presentation & the Autism paper.

Finally remember Dr N took out $500 000 of debt for the Suramin study. How many scientists would do that?