Queensland Government: Gold Coast researchers make chronic fatigue breakthrough

[A.B.]

I agree. In my case I also have POTs and for years have suffered what seem like quite severe hypoglycemic episodes, which I feel are not POTs related but energy and blood sugar related and what I feel make a lot more sense given the latest research on our inability to metabolize sugars.
These particular symptoms are complete relieved by having a meal and get worse the longer I go without food.

It doesn't take high tech science and instruments to see the obvious!

 

[Valentijn]

I am convinced that when people with ME are saying they have hypos (but they have normal blood sugars) that it is actually symptoms of dysautonomia that they are experiencing.

OI and false hypos feel very different to me. The false hypos make me feel very shaky. And OI never makes me feel like I need to eat ... if anything, it has the opposite effect.

I've never had the symptoms I get from false hypos before. It doesn't resemble anything I've had with ME/CFS. Though I do suspect that ME/CFS interferes with recovering quickly from false hypos.

 

[simeyss]

My, hopefully unjustified, fear is that overhyping these results will come back to bite us if it can't be replicated. The BPS crowd would just love to be able to point at something as proof that there is no biomedical basis for ME. Nothing has changed my opinion, I much prefer how Fluge and Mella are going about things, explaining a lot and making few claims, instead of this group seeming to claim a lot based on very little.

I agree. Not to mention the fact that this group are exceptionally good at gobbling up huge amounts of the available funding for ME/CFS in Australia, leaving other groups doing excellent work (eg: Armstrong, McGregor & co's metabolomics work) out in the cold. Funders and donors seem to believe the hype.

 

[simeyss]

That said, they've been forced to work with small samples of patients, probably due to limited funding. That's the other reason I'm glad to see them making waves - that's how researchers get funding, as we've seen from the BPS school in the UK. And with more funding, they should be able to conduct larger and better studies with reliable results.

Unlike many other groups, NCNED is well-funded. They've received $1.6m from Qld gov't since 2008, almost $1m from Mason Foundation, $4m (over 5 years) from Stafford Fox Medical Foundation, and the Alison Hunter Foundation now fundraises exclusively for NCNED. Those are just the publicly known grants. With the money they have raised, they should be able to undertake studies with larger cohorts.

 

[Mel9]

Unlike many other groups, NCNED is well-funded. They've received $1.6m from Qld gov't since 2008, almost $1m from Mason Foundation, $4m (over 5 years) from Stafford Fox Medical Foundation, and the Alison Hunter Foundation now fundraises exclusively for NCNED. Those are just the publicly known grants. With the money they have raised, they should be able to undertake studies with larger cohorts.

NCNED are very well meaning talented scientists who deserve their funding

That is not to say that the excellent Armstrong group shouldn't receive adequate funding too.

 

[simeyss]

NCNED are very well meaning talented scientists who deserve their funding

That is not to say that the excellent Armstrong group shouldn't receive adequate funding too.

I agree that they are well meaning talented scientists. My point was that the reason for their small samples wasn't to do with lack of funding. They are well-funded, and hopefully this will yield some terrific results. Right now, based on the published studies, these findings are preliminary.

 

[thane17]

Maybe the "thing" in the serum is causing the receptors dysfunctioning and nothing wrong with them structurally. Griffith team should repeat the tests with ME/CFS cells in healthy serum.

Great idea. As I understand it nobody has published on the healthy serum sick cells, and sick serum healthy cells phenomena yet, so I think that should happen anyway.

 

[Paintmyturquoise]

I know the researchers needs funding, but this is stinky journalism.

I think it's on point PR.

That said, they've been forced to work with small samples of patients, probably due to limited funding.

As others have said, the researchers don't need funding, they received the largest ME/CFS grant ever...

The 'newness' came from a study from nov published this year

I'd expect there are more studies to come and these small preliminaries are just markers

 

[Marky90]

I think it's on point PR.

Personally I would reserve the term "breakthrough" for the situation when we know that the findings are causative for our symptoms - And when this has been independently replicated and compared with similar diseases.

Don`t get me wrong though, I dont mind the PR for a change either lmao

 

[aimossy]

I find it interesting that no media coverage of this asked for independent researcher opinion considering the claims. It hasn't been balanced coverage.

I feel it is unfortunate that there are a lot of people out there especially in our FB community now thinking there is a definitive test for ME/CFS. I also feels like a bit of irresponsible marketing and seems even slightly suspect when your wanting to commercialize this early in the peice when it isn't even clear if this finding has relevance in me/cfs pathophysiology. The list can go on.

Here is an article that popped up today from last year where they are talking about a screening test not a diagnostic test and looking for a partner to invest. They even say it needs no refinement yuge claims! Maybe they have frighteningly good papers to come that match such confidence. http://www.iflscience.com/health-and-medicine/chronic-fatigue-test-ready-commercialization/

I wish some independent researchers would comment on the claims personally. It's not good having patients being led down the garden path if these claims don't match what's published so far. Even if there is some possible meat in the findings.

 

[A.B.]

This may have been mentioned already:

TRPM3
It is persuasive to note that TRPM3 channel is activated by sphingosine. In transiently transfected HEK293 cells, TRPM3 was found to be sensitive to sphingosine and its precursor dihydrosphingosine. Another important finding was that responsiveness to sphingosine was limited to TRPM3, whereas sphingosine was ineffective in activating HEK293 cells expressing TRPC3, TRPC4, TRPC5, TRPV4, TRPV5, TRPV6, or TRPM2. There are various drugs which influence TRPM3-mediated cellular activities. Mefenamic acid selectively inhibits TRPM3-mediated calcium entry after treatment of cells with pregnenolone sulfate. This selectivity was further confirmed using insulin-secreting cells as treatment of cells with pregneno-lone sulfate resulted in activation of TRPM3 which was inhibited by mefenamic acid (Klose et al. 2011). On a similar note, troglitazone and pioglitazone also inhibited TRPM3 (Majeed et al.2011).

http://sci-hub.cc/10.1007/s00251-011-0570-4

Sphingosine is a component of sphingolipids. LEt's again look at what Naviaux had to say about sphingolipids:

The dominant finding from the pathway analysis was that sphingolipid abnormalities constituted close to 50% of all of the metabolic disturbances associated with CFS in both males and females.

Coincidence or not?

 

[OverTheHills]

warning - no science background and brain function of a caterpillar - this may be a very very stupid question.

@A.B. mentioned mefanemic acid's effect on TPRM-3 mediated calcium uptake. I used to take loads of this as it was an effective painkiller for my severe endometriosis pain. Might this be a useful drug or a problem drug for ME sufferers?

Thanks

 

[kangaSue]

Sphingosine is a component of sphingolipids. LEt's again look at what Naviaux had to say about sphingolipids:

@A.B. These get discussed quite extensively starting from about page 25 in this thread http://forums.phoenixrising.me/inde...n-in-myalgic-encephalopathy-cfs.48446/page-25

 

[hixxy]

I agree that they are well meaning talented scientists. My point was that the reason for their small samples wasn't to do with lack of funding. They are well-funded, and hopefully this will yield some terrific results. Right now, based on the published studies, these findings are preliminary.

This is untrue. NCNED wanted to start in vitro testing drugs on these TRP channels back in 2015 but only received funding to start in December last year. So they were not swimming in funding as you are implying.

 

[J.G]

They seem to be going all in on this TRPM3 receptor dysfunction. I don't know how I feel about that. If we've learned anything at all from the Navuaux and Fluge&Mella papers it'd be "heterogeneous causes, (more or less) homogeneous presentation". It's certainly possible TRPM3 is (part of) a cause, but I find it a little bit fanciful to think it must be the cause.

More so, I worry the researchers may be digging a hole for themselves much like the BPS school did with PACE, publicly declaring full faith in a hypothesis before the evidence is there. The risk is ultimately eating your own words or post-rationalising findings in the face of contradictory evidence. Both hurt the patient community. I'm sure that's not what the researchers intend to do, yet much is at stake here, so I'd advise caution in public pronouncements to at least keep the media from overhyping and prevent this thing from blowing up in our faces eventually.

 

[simeyss]

This is untrue. NCNED wanted to start in vitro testing drugs on these TRP channels back in 2015 but only received funding to start in December last year. So they were not swimming in funding as you are implying.

They are the most well-funded ME/CFS research group in Australia by far. They have received $1.6m from the Qld government, more than $800k from Mason Foundation, and the Alison Hunter Foundation is now fundraising exclusively and proactively for them. They were not want for funds prior to the Stafford Fox Medical Foundation grant.

 

[simeyss]

They seem to be going all in on this TRPM3 receptor dysfunction. I don't know how I feel about that. If we've learned anything at all from the Navuaux and Fluge&Mella papers it'd be "heterogeneous causes, (more or less) homogeneous presentation". It's certainly possible TRPM3 is (part of) a cause, but I find it a little bit fanciful to think it must be the cause.

More so, I worry the researchers may be digging a hole for themselves much like the BPS school did with PACE, publicly declaring full faith in a hypothesis before the evidence is there. The risk is ultimately eating your own words or post-rationalising findings in the face of contradictory evidence. Both hurt the patient community. I'm sure that's not what the researchers intend to do, yet much is at stake here, so I'd advise caution in public pronouncements to at least keep the media from overhyping and prevent this thing from blowing up in our faces eventually.

I agree. Well said.

 

[FMMM1]

Their findings don't seem to match with what Stanford is seeing. According to Ron Davies the problem is in the serum, not the cells.

I agree that this is confusing.
In this paper the Griffiths team have published data indicating that there is a problem re calcium regulation by TRPM3 receptors in B-cells, correct?
Fluge and Mella have published data indicating that there's something in plasma from people with ME/CFS which is causing B-cells to switch from "normal" state (burning glucose) to "threat" state burning certain types of protein, correct?

How could B-cells with faulty TRPM3 receptors suddenly be OK in healthy plasma and vice versa?

I still think the Griffiths team have made a fundamental breakthrough but I've no idea when we will see:

1. a diagnostic test e.g. based on errors in TRPM3 gene; or
2. treatments e.g. based on drugs currently approved for similar conditions.

 

[alex3619]

@FMMM1 We also might consider the possibility that there is mixed accuracy here. For example, the TRPM3 snp findings might be misleading, but the calcium problem might be accurate. Instead, we might find that the putative inhibiting factor is inhibiting calcium regulation. If so then studies on our NK cells in serum and out of serum will differ. As you pointed out this does need to be investigated. Instead of a TRPM3 snp test we might find a TRPM3 function test is the answer.

 

[alicec]

the Griffiths team have published data indicating that there is a problem re calcium regulation by TRPM3 receptors in B-cells,

They found a difference in NUMBERS and RESPONSE of TRPM3 receptors on NK cells, they didn't actually study the receptors themselves. The studies were not done in B cells, though there is no reason to think the results peculiar to NK cells - the receptors are present on various cells/tissues. They just chose to study NK cells.

How could B-cells with faulty TRPM3 receptors suddenly be OK in healthy plasma and vice versa?

The study did not show that there is anything inherently faulty about the receptors. The authors suggest this is the case because it gives their results more potential significance. But this is an assumption based on two thin pieces of evidence.

As is discussed here, neither piece of evidence is convincing. The first actually doesn't exist - there are no differences in SNPs when adequate statistics are used for analysis and the second, altered NK function, is not a consistent finding in CFS/ME. At this point there is no evidence that the receptors are faulty.

The study results could be perfectly compatible with a serum factor modifying the response of the TRPM3 receptors, and NK cell activity differences could also be explained by the effect of a serum factor - as discussed in that same link.