Jarred Younger on Neuroinflammation in ME/CFS and Fibromyalgia

[leokitten]

You might equally find that labs or researchers studying autoimmunity only focus on that area; but that itself is not any reason to criticize the autoimmune hypothesis of ME/CFS. Science by its nature if often divided into specialties.

@Hip I think I was misunderstood here and sorry for the poor choice of words. I certainly know that in science research groups typically focus on a particular area.

What I meant in my text and criticism of Dr. Younger is something that is seen time and time again that I don't enjoy seeing other scientists do. Dr. Younger wrote his research proposals and grants to study ME/CFS (and other diseases) on the hypotheses we are talking about here, that he believes the root cause of this disease and other related diseases is neuroinflammation. He received quite a bit of money from the NIH to do so and built his entire lab from this.

Now when the ME/CFS community is seeing a growing body of very compelling evidence that ME/CFS is possibly some kind of B-cell driven autoimmune disorder what does Dr. Younger do? He attempts to monkeywrench all these findings into his own hypothesis and beliefs on the root cause of this disease. Honestly I think a lot of what he said is very poorly thought out and doesn't make sense.

I do believe chronic microglial activation plays a role in the pathology of ME/CFS just like it plays a role in a number of other diseases that at their root have nothing to do with the brain. I think Dr. Younger would serve himself better sticking to that line for now until he can actually prove otherwise.

You may be taking microglial activation inhibitors, but unfortunately I don't think there is any evidence in any given patient that these drugs or supplements are indeed inhibiting microglia.

@Hip you've read my posts, you know I'm taking many of the drugs and supplements you've nicely put together in that other thread. I agree there isn't irrefutable evidence in patients that microglial activation is inhibited by these but there is a lot of foundational evidence and my personal belief is if I'm taking 8 potent pharmaceutical drugs and many more supplements that are on your list for a long time now and stil not being able to manage this disease to live a somewhat normal life then this isn't the whole picture.

I think you even tried Ibudilast which is a very potent medication and said it did nothing for your ME/CFS. There is a lot of evidence that Ibudilast does turn off microglial activation, enough evidence that NIH NIDA is funding clinical trials for its use in methamphetamine and cocaine addiction, two conditions which are known to have significant neuroinflammation which is believed to contribute to the addiction, withdrawal symptoms, and overall disease.

Even if they were, is inhibiting microglia the right approach to tackling brain inflammation? There are many things going on within brain inflammation, including changes to astrocyte function. Some researchers speculate it is extracellular glutamate build-up from brain inflammation that is the problem, and this involves microglia which release glutamate as well as astrocytes which help clear it.

Agreed, maybe there is something more subtle that is being missed.

I myself had a lot of success in eliminating my severe generalized anxiety disorder using supplements that targeted brain inflammation (see this thread). And when I began regularly taking these supplements, I noticed my ME/CFS symptom slowly but significantly improved, as this may have been a result of their anti-neuroinflammation effect.

I completely agree. Soon after I got ill with ME/CFS the disease caused me to have strong anxiety symptoms which I never had before in my life and this came with all the other "wired by tired" symptoms. After taking all the anti-neuroinflammatory drugs and supplements I've mentioned in my thread these symptoms reduced over time to the point of being almost gone. But you are reinforcing my original point:

So many of us have taken combinations of drugs and supplements that are known to potently inhibit microglial activation etc. but they just don't work in a big enough way to be considered treatment. If ME/CFS was a putative neuroinflammatory disease then many of us would be gone into remission or significant recovery by now and for all you taking such drugs I know you feel like I do, they possibly have some effect on some symptoms but they aren't disease modifying at all.

After taking targeted anti-neuroinflammatory drugs/supplements to eliminate many of your neurological issues caused by ME/CFS have you experienced a significant enough recovery to the point where your disease is manageable and you can work and be more active again? I would guess the answer is no.

I also still have ME/CFS, it didn't go anywhere and these anti-neuroinflammatories clearly for you and for me only reduced those symptoms but were not disease modifying at all.

 

[Hip]

What I meant in my text and criticism of Dr. Younger is something that is seen time and time again that I don't enjoy seeing other scientists do. Dr. Younger wrote his research proposals and grants to study ME/CFS (and other diseases) on the hypotheses we are talking about here, that he believes the root cause of this disease and other related diseases is neuroinflammation. He received quite a bit of money from the NIH to do so and built his entire lab from this.

Now when the ME/CFS community is seeing a growing body of very compelling evidence that ME/CFS is possibly some kind of B-cell driven autoimmune disorder what does Dr. Younger do? He attempts to monkeywrench all these findings into his own hypothesis and beliefs on the root cause of this disease. Honestly I think a lot of what he said is very poorly thought out and doesn't make sense.

Pretty much every scientist involved in researching ME/CFS (or any other disease) tends to do so from the perspective of their own expertise and interests. And this is good thing, because it means you have numerous researchers from all different fields examining a disease from different angles; one or more of those angles may yield results. One would not want to abandon the microglial perspective just because at the moment there is some excitement about an autoimmune connection to ME/CFS.

But you seem to be suggesting that because of this current excitement in autoimmunity, we should drop everything else.

I used to be a bit like this when I first started reading about ME/CFS. Whatever theory I was reading on a particular month dominated my thoughts, and that theory seemed to me to be the answer, and I would be dismissive of other theories — until the next month, of course, when I had moved on to another theory. But after many years of reading dozens of different ME/CFS theories and etiologies, I have lost my monomania, and become broadminded with regards possibilities.

A complex disease like ME/CFS is likely going to involve many areas of physiology anyway, so even it were to be conclusively demonstrated that there is an autoimmune aspect to this disease, that may be just be part of what is amiss in the body in ME/CFS.

After taking targeted anti-neuroinflammatory drugs/supplements to eliminate many of your neurological issues caused by ME/CFS have you experienced a significant enough recovery to the point where your disease is manageable and you can work and be more active again? I would guess the answer is no.

My ME/CFS has improved significantly as result, I think, of various drugs and supplements I am taking, many of which are anti-inflammatory, although I do not know if these anti-inflammatory supplement are responsible for my improvements.

In any case, I don't think that is any kind of argument against a possible neuroinflammatory pathophysiology involved in ME/CFS.

I have also taken drugs like oxymatrine that can be effective against enteroviruses, but without seeing any improvements in my symptoms. Does that mean that I don't have an enterovirus infection, or that ME/CFS is not associated with enteroviruses? Of course not.

Equally, I have tried out some of my own experimental anti-autoimmunity protocols, including trying cocktails of Th17-inhibiting drugs and supplements, which made me feel worse; and estriol, a major hormone in pregnancy, which promotes tolerogenic dendritic cells that protect against autoimmunity. 1 This did not help either. Does that mean I can rule out an autoimmune etiology? Of course not.

 

[Hip]

There are also other funky things you can do with microglia. I found it fascinating that a bone marrow transplant was shown to eliminate mental illness in mice.

Microglial cells are manufactured in the bone marrow, and then migrate to the brain via the bloodstream, so this is likely how such transplants are curing mental illness, by replenishing the microglia in the brain with a healthy stock of new cells.

It would be interesting to see what a bone marrow transplant might do for a ME/CFS patient. In reality, this is not going be investigated, because of the severe risks and complications involved in bone marrow transplantation (though I wonder if there have been any cancer patients who also have ME/CFS that have received a bone marrow transplant?)

However, it occurred to me that something analogous to bone marrow transplantation might work for ME/CFS, for example, where you culture healthy microglia cells in vitro, and then inject these cells into the bloodstream, where they would presumably migrate as per normal into the brain, thereby replenishing the microglia in the brain with healthy microglial cells that have not been primed to become over-sensitive and over-active.

That might work not only for ME/CFS, but many mental or neurological diseases where chronic microglial activation is involved.

 

[leokitten]

Pretty much every scientist involved in researching ME/CFS (or any other disease) tends to do so from the perspective of their own expertise and interest. And this is good thing, because it means you have numerous researchers from all different fields examining a disease from different angles; one or more of those angles may yield results. One would not want to abandon the microglial perspective just because at the moment there is some excitement about an autoimmune connection to ME/CFS.

But you seem to be suggesting that because of this current excitement in autoimmunity, we should drop everything else.

Of course not. Please re-read my post as I've never suggested this. Of course it's great that scientists from different areas study this disease from their own perspective and research areas. What I was criticizing in my two posts is Dr. Younger's response to the growing body of evidence supporting autoimmunity. What he is doing is:

1. Trying to take this evidence and construct an explanation as to why it still fits his hypothesis and field of research
2. Continuing to push the belief that his hypothesis explains the root cause of the disease, even with very little evidence

Sorry but I am critical of these actions, it's really sad when scientists do this. This is what I was saying (as well as others) about "not invented here" syndrome. Dr. Younger should very much continue to study neuroinflammation and its role in ME/CFS. But he should be a bit more modest and until he has more evidence to the contrary he should stay with the line that he doesn't know what role neuroinflammation plays and definitely stop making to far fetched explanations so that the Norway results might fit his hypothesis and area of research.

I used to be a bit like this when I first started reading about ME/CFS. Whatever theory I was reading that month dominated my thoughts, and that theory seemed to me to be the answer, and I would be dismissive of other theories — until the next month, of course, when I had moved on to another theory. But after many years of reading dozens of different ME/CFS theories and etiologies, I have lost my monomania, and become broadminded with regards to possibilities.

Look at my post history. For the first year (late 2013 - mid 2014) based on all the literature I read and knowledge I'd acquired I was leaning more towards the infectious theory. This was years after Fluge/Mella's first two Rituximab papers (2009, 2011) and I had read those and associated evidence but reserved judgement. Only as more evidence was published showing that the infectious theory was likely a dead end for many if not most PWME and with more robust evidence coming from Norway did things change for me. I've never been on any other bandwagon.

A complex disease like ME/CFS is likely going to involve many areas of physiology anyway, so even it were to be conclusively demonstrated that there is an autoimmune aspect to this disease, that may be just be part of what is amiss in the body in ME/CFS.

I more believe in Occam's razor. Of all the other diseases that effect humans where do we see that pattern of etiology? Where the causes of the disease involve so many different systems? With virtually every disease it comes down to one or two causes and systems of the body driving the disease and yes as a consequence causing other systems to go awry and play a subsequent role. But those other systems are just noise and if we treat the most upstream cause it also treats downstream effects.

No one should get the idea that ME/CFS is complex because after decades the scientific community has discovered next to nothing. Multi-system diseases like ME/CFS have just seemed complex to us because:

1. Most importantly we haven't spent any real money studying them
2. There aren't any easy-to-find and reliable biomarkers
3. They cause a wide variety of symptoms affecting many areas of the body which confuses clinicians and researchers and provides few clues as to the pathology

A very serendipitous thing about the work coming from Norway is that they essentially leapfrogged decades of research. Instead of going through the arduous process of basic research, target and drug development and/or screening, preclinical studies with animal models, then human studies and all phases of clinical trials they were able to make a huge discovery giving us many clues while at the same time going full speed towards drug approval. In all the other areas of ME/CFS research with their current state of knowledge its going to be another 20+ years before an FDA approved drug gets to the market.

My ME/CFS has improved significantly as result of various drugs and supplements I am taking, many of which are anti-inflammatory, although I do not know if these anti-inflammatory supplement are responsible for my improvements.

In any case, I don't think that is any kind of argument against a possible neuroinflammatory pathophysiology involved in ME/CFS.

Again, as I've stated I believe that neuroinflammation has a role in ME/CFS just like it has in many other diseases that are not neurological, just my money isn't on it being the etiology of ME/CFS.

 

[msf]

What evidence is there against an infectious theory, rather than for an autoimmune one?

 

[Hip]

1. Trying to take this evidence and construct and explanation as to why it still fits his hypothesis and field of research
2. Continuing to push the belief that his hypothesis explains the root cause of the disease, even with very little evidence

Sorry but I am critical of these actions, it's really sad when scientists do this.

Perhaps @Jonathan Edwards might weigh in here, but from reading many areas of science out of my own interest, it always seems that when a scientist is running with a particular hypothesis, they usually try their best to figure out how the observed facts can be explained by their hypothesis. The hypothesis is their baby, and so naturally they work hard to try to make sure it has the best start in life, so to speak.

You can rest assured that many other scientist are going to be skeptical and critical of your hypothesis or theory, so if you don't work to support your hypothesis, nobody else will.

 

[leokitten]

What evidence is there against an infectious theory, rather than for an autoimmune one?

One major example:
http://phoenixrising.me/archives/19083

 

[msf]

So there's evidence against it being a virus.

 

[msf]

Are you also aware that the same group (possibly just the Stanford group actually) are going to release another study of pathogens in ME, and they said in the Stanford 2015 ME/CFS newsletter that there were some exciting results?

 

[leokitten]

So there's evidence against it being a virus.

Sorry I found a link and edited my post. No I think Lipkin was looking for any pathogen and has yet to find any evidence.

 

[msf]

Yeah, he was looking for any, but he's only reported on the virus data yet, and even that hasn't been published.

 

[leokitten]

Are you also aware that the same group (possibly just the Stanford group actually) are going to release another study of pathogens in ME, and they said in the Stanford 2015 ME/CFS newsletter that there were some exciting results?

Yes I think it's Montoya et al and am excited to see what they have to say.

 

[msf]

Me too, it'd better not be bloody anelloviruses!

 

[leokitten]

Me too, it'd better not be bloody anelloviruses!

LOL, honestly I have a feeling it's going to be some exotic virus... which means very little progress for us

 

[msf]

Could be, but if it is it might well be whatever Lipkin has been finding in ticks, which would be a pointer, at least.

 

[halcyon]

The fact that they're bringing in a gastroenterologist might hint that they found an enteric pathogen.

 

[msf]

They are also bringing in Lyme experts...

This could be because:

a.) They suspect Lyme in some ME patients.
b.) They have found Lyme in some ME patients.
c.) They think ME is too easy and they want a real challenge.

 

[JPV]

Kenny de Meirleir has also started focusing more on Lime Disease.

 

[Scarecrow]

They are also bringing in Lyme experts...

This could be because:

a.) They suspect Lyme in some ME patients.
b.) They have found Lyme in some ME patients.
c.) They think ME is too easy and they want a real challenge.

Oh, good. I do like a multiple choice test.

 

[msf]

Haha, I'm sure they should be four in multiple choice but I couldn't think of a fourth.