Dr Ron Davis - Updates on ME/CFS research - September 2019 onwards

Perrier said:
new announcement/interview with Dr. Ron Davis today
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This is mostly on the tryptophan metabolic trap. They have been trying to disprove it and have failed. Its been slowed by lack of fresh blood due to the pandemic, apparently frozen blood is unsuitable. There is preliminary data suggesting but not proving that the trap can happen in humans. More detailed data is from genetically modified yeast, in which they have been able to induce the trap and are now screening drugs to see if they prevent this in yeast. Some candidates have been found.

The emphasis is now on IDO1 more than IDO2. IDO2 may be less important than they thought.

Several other metabolic traps await analysis.

Any candidate drugs will of course have to be tested on patient cells in due course. I am not sure this was explicitly stated but was at least implicit in the discussion.
 
Crossposted with Alex. Between us I think we covered most of it.

I have just watched it. It's a update on the research on the IDO1, IDO2, kynurenine, tryptophan metabolic trap hypothesis.

He reminds us that this is just one of many possible metabolic traps, and that the task at this stage is to take this particular one and design experiments to try to disprove the hypothesis, so then they know it's not true and can move on to something else. If they can't disprove it, then it may be true at least for some patients.

So far they have put the relevant human gene in yeast which is often used in genetic experiments because it's easy to do. Their first tests didn't disprove the hypothesis, so they are now testing some FDA approved drugs to see if any of them can reverse the trap. This is done by putting the cells in the trap, then adding the drug, and if they start growing again, then it may be because it reverses the trap or it may be some other reason. So far they have found several drugs that reversed the effect in the yeast, and have more to test.

They are now starting to test the drugs on patients' blood cells which have to be freshly collected.

I hope I've got all that right, it's written from memory after watching it once.
 
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Thanks for summaries.

(Just a personal note: I wish that working time lines were also offered. These could be changed as things develop, but I do find the absence of working time lines very hard to take. I have been told that science doesn't work this way. But many years ago when I worked in the control lab for Merck there were always time lines in all the labs, and indeed these were often changed, but time lines were there and kept all us trying to adhere to them.)
 
In this case from what Ron described, it's being done with 'make do and mend' old equipment by one person, for whom it's probably only a small part of her job. You can't put a time line on that if the old equipment uses out of date computer progams written by someone who no longer works there. Finding fixes takes as long as it takes.
 
Trish said:
In this case from what Ron described, it's being done with 'make do and mend' old equipment by one person, for whom it's probably only a small part of her job. You can't put a time line on that if the old equipment uses out of date computer progams written by someone who no longer works there. Finding fixes takes as long as it takes.
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With the greatest respect, we are talking about America here, and this is Stanford university and this researcher is top in the world. Is this a sign of the decline of America? I appreciate your observation Trish, I really do, and truly understand the implications, but this is not some rare illness, and I am truly puzzled that such a prestigious institution cannot help out this hard working selfless brilliant well known researcher. Just a personal opinion.
 
Trish said:
In this case from what Ron described, it's being done with 'make do and mend' old equipment by one person, for whom it's probably only a small part of her job. You can't put a time line on that if the old equipment uses out of date computer progams written by someone who no longer works there. Finding fixes takes as long as it takes.
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I have lost touch with Omf research and with this specific research. But my impression, which may be wrong, is that the metabolic trap is a main focus if not the main focus at Stanford. And that OMF brings in $5 million a year. I don’t understand how that squares with somebody working part time with old equipment to tackle a key priority. Clarification appreciated
 
Simon M said:
I have lost touch with Omf research and with this specific research. But my impression, which may be wrong, is that the metabolic trap is a main focus if not the main focus at Stanford. And that OMF brings in $5 million a year. I don’t understand how that squares with somebody working part time with old equipment to tackle a key priority. Clarification appreciated
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The logical assumption would seem, at least to me, that the people who hold the purse strings for the OMF aren't convinced of the value of this work and so prefer to fund other efforts, such as the recently announced sleep study.
 
Ron says that the work on this hypothesis started when it was found that all of the people on their severe ME/CFS study had a mutation in the IDO2 mutation, and they found the same problem in a large number of other patients. He goes on to say
'Now, many people have found that there are people that have this disease that don't have mutations in IDO2. In the population, many people have a mutation in IDO2.'

I accept that those findings aren't necessarily the end of the theory - maybe the trap can happen despite the genes, maybe other genes can provide an exit from the trap. But it's the first clear statement I've heard acknowledging that a IDO2 mutation isn't found in 100% of people with ME/CFS. And that seems important. Back in May, Ron and Janet were talking about the IDO2 mutation, and I commented:
Hutan said:
Janet says that 70 patients have been tested for the IDO2 mutation and all but one (who is an 'unusual case') has the mutation.
(Has this been replicated by any other researcher? Surely it wouldn't be so hard to check this finding in other patient populations, and surely that is important to do? If it could be replicated, that would do a great deal for OMF's credibility.
There's an edit straight after Janet talks about the 70 patients, and suddenly the presenter is laughing and Ron is talking about tryptophan in yeast cells. So Ron doesn't confirm the finding of the mutation in all patients tested so far.)
There was some discussion about yeast cells that have been modified to have a functional human IDO1 and no other way of producing tryptophan, being used to screen drugs.
Ron thinks the tryptophan trap is the primary cause of ME/CFS. He thinks a drug fixing the trap could cure patients overnight.
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Just to add, Ron closes this November update with
"So, I'm kind of excited about this. This is a possibility. But again, all we're trying to do is to say the metabolic trap is not right so we can move on. but so far we have failed to do that. And so we are continuing to pursue it. For those people who think that we have ruled out the metabolic trap, we have not.

Keep in mind we are also identifying a number of other metabolic traps that could possibly be important in this disease and those traps will be explored when we have the capacity to do so."

So that is quite a shift from the May presentation where Ron was much more certain.
 
Hutan said:
Ron says that the work on this hypothesis started when it was found that all of the people on their severe ME/CFS study had a mutation in the IDO2 mutation, and they found the same problem in a large number of other patients. He goes on to say
'Now, many people have found that there are people that have this disease that don't have mutations in IDO2. In the population, many people have a mutation in IDO2.'

I accept that those findings aren't necessarily the end of the theory - maybe the trap can happen despite the genes, maybe other genes can provide an exit from the trap. But it's the first clear statement I've heard acknowledging that a IDO2 mutation isn't found in 100% of people with ME/CFS. And that seems important. Back in May, Ron and Janet were talking about the IDO2 mutation, and I commented:
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He is probably referring to the UK Biobank data - it was analyzed and the IDO2 mutations are not more frequent in ME/CFS patients than they are in controls. This was acknowledged by Janet Dafoe in a tweet, which was something like "yes Ron has looked at the UK biobank and there is no difference between patients and controls". Her justification for this was that in her opinion the patients who participated in the UK biobank study do not really have ME/CFS and so that's why they don't have the mutation.

My guess is that Linda Tannenbaum looked at this and decided the metabolic trap hypothesis was not worth funding anymore, and that is why there has been a huge delay and Ron Davis has to make do with old broken equipment and part time work.
 
Andy said:
The logical assumption would seem, at least to me, that the people who hold the purse strings for the OMF aren't convinced of the value of this work and so prefer to fund other efforts, such as the recently announced sleep study.
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I'd really like to see some more co-ordinated messaging and research at this point. There is a lack of clear strategy (at least to me). Evidently there are divergent views about priorities (how else to explain this?), or we are only being given a partial picture. As someone who would potentially donate to OMF, I find these discrepancies offputting as I feel like I am missing an overall plan with clearly defined goals and (rough) timescales.
 
The stunning part of this update is that they are trying to disprove the theory. So much research into ME has just been dropped and either forgotten or people say it did not work out when it was just that the miniscule funding ran out, no funds were made available for large scale trials, the researcher died or became ill or something changed politically (thinking specifically about the NIH work into diastolic heart failure where the last work was not published and nothing more was heard.)

If we know it does not work we can move on. It is so different from all the confirmation studies done by the BPS.

I suspect that Ron Davis is desperate to find a treatment for his son while he can so does not have the luxury of time to wait for pleading his case to outsiders. His son being involved means he may be overoptimistic that there will be a simple cure but it surely means he must believe this has promise.
 
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