Montreal ME/CFS II: Stopping PEM, the Antibody Subset and Unutmaz’s Big Surprise

[Gingergrrl]

I searched in case this link was already posted but couldn't find it. It is from Cort's blog /Simmaron Research re: the recent Montreal Conference. I am particularly interested in Dr. Scheibenbogen's autoantibody research so I am quoting some of that portion (but there is a lot more to read on other topics, too)!

http://simmaronresearch.com/2018/05/montreal-ii-stopping-pem-antibody-subset-unutmazs-big-surprise/

Carmen Scheibenbogen
Scheibenbogen is a mover and shaker. She’s published six papers on ME/CFS in the past three years, is a leader in the Euromene Group, has been talking to pharmaceutical companies about drugs, and is organizing a fatigue conference in Germany to get some good networking going.

Dr. Rowe called Dr. Scheibenbogen’s antibody findings one of the most exciting ME/CFS research findings in years. Peter Rowe called her recent autoantibody papers one of the most exciting recent developments in the field. Scheibenbogen, interestingly, got the idea to do those studies from similar recent findings in POTS (postural orthostatic tachycardia syndrome).

Scheibenbogen rattled off some of the commonalities between autoimmune diseases and ME/CFS. Both predominantly affect women, both are often triggered by an infection and she’s found a high family history of autoimmunity in ME/CFS. Plus, Epstein-Barr virus – a common trigger in chronic fatigue syndrome (ME/CFS) – invades B-cells which are the main drivers of autoimmunity. The difficulty ME/CFS patients and others have fighting off the virus when exposed to it later in life apparently gives the immune system plenty of opportunity to make a mistake and begin attacking our own tissues.

Rituximab
Rituximab is used to treat autoimmune diseases. The Rituximab ME/CFS trial’s main endpoint failed but Scheibenbogen asserted that we shouldn’t count Rituximab out at all. She believes, and she would know, because she’s studied Rituximab patients, that Rituximab will be shown to be effective in a subset of patients. An effective treatment in a subset of ME/CFS patients would be a big deal – particularly for those patients.

Scheibenbogen found increased levels of antibodies in about 40% of ME/CFS patients, and Bergquist’s study that is currently underway thankfully had similar results. At least right now it appears that the 40% figure is solid, but the search for antibodies in ME/CFS is not over. When I asked Scheibenbogen if other antibodies might be involved, she said, yes, other antibodies probably will apply. If that’s so, that 40% number could go up. Scheibenbogen noted that the B2 and muscarinic antibodies that have been showing up in ME/CFS are part of a larger network.

Interestingly, these are not autoantibodies; they’re natural antibodies which affect breathing, the circulation and the gut. Their high levels in ME/CFS appear to be throwing those systems off.

Immunoadsorption
Immunoadsorption is another possible immune treatment for chronic fatigue syndrome (ME/CFS). Immunoadsorption, which is similar to, but more effective than plasmaphoresis, removes IgG autoantibodies from the blood. It’s an expensive treatment – about $20,000.

Like Rituximab it will probably be effective in a subset of patients. Scheibenbogen’s small immunoadsorption trial of ME/CFS patients with specific autoantibodies found that the treatment did what it was supposed to do – it significantly reduced antibody levels for at least six months.

Symptoms improved in most patients and some patients completely recovered. Three are still in remission a year after the treatment ended. One person completely recovered for 6-7 weeks but then relapsed. After she relapsed, she could hardly walk again. The trial suggested that Scheibenbogen is on the right track with her autoimmune studies. The fact that POTS is so prevalent in ME/CFS and has similar autoantibody issues suggests that the outcome is not such a surprise.

The trial was small and carefully curated to those with high antibody levels but most patients improved and some recovered. A follow-up study is beginning. If that works out, Scheibenbogen hopes for a big trial that will settle the issue definitively. In a good sign, she reported that the company that produces the immunoadsorption treatment (not available in the U.S.) is quite interested in ME/CFS.

(Even if the treatment is not available in the U.S., a successful trial could do a couple of things: it could prompt the company to make the treatment available in the U.S., and it would surely enhance autoimmunity research. We’ll see what happens, but if we can come up with several treatments – each of which is effective in a subset of patients – we’ll start to whittle the disease down.)

 

[Diwi9]

@Gingergrrl - Thank you, been waiting for Cort to post the second part of Montreal!

 

[msf]

It's already possible to stop PEM, but high amounts of dca cause peripheral neuropathy, so hopefully they're coming up with a less problematic alternative.

 

[msf]

PEM caused by lactic acid build up, that is.

 

[Seven7]

What is DCA? Never heard of it for PEM

 

[msf]

There's a whole thread and pilot study on it, just Google it. DCA stands for dichloroacetate. If you want to know how it might work, I wrote a blog about how I think ME works, and DCA fits nicely with that (once you know that it is also an mtor inhibitor).

 

[Murph]

Both part of @Cort's montreal write-up are worth a read.

I'm interested in Unutmaz and his T-Cell work that finds a link to the gut certainly seems like it could be a missing link for us.

Unutmaz is a T-cell guy. He knows that bacterial metabolic by-products trigger unusual T-cells called MAIT T-cells (Mucosal associated invariant T cells) to get into action. Once these cells, which are found in our gut lining, liver, lungs, etc., come across those metabolites, they secrete pro-inflammatory cytokines. Those cytokines turn monocyte cells into hairy monsters called macrophages which then gobble up the bacterial-infected cells.

MAIT cells, then, play a key role in turning on our immune response to the bad bacteria that can live in our guts. They apparently lurk in the gut lining as a kind of last line of defense against those bacteria getting into our blood stream and invading the rest of the body.

Unutmaz found that a high percentage of MAIT cells had been repeatedly activated in ME/CFS patients – suggesting a plethora of bad bacteria was present. In true ME/CFS fashion, Unutmaz also found that ME/CFS patients’ MAIT cells were activated — but “punked out” at the same time. (A wired and tired immune cell?). Seemingly exhausted by the continual stimulation, they (like their natural killer cell cousins) had problems killing infected cells. That hearkened back to the Lipkin/Hornig immune finding of activated immune systems in early-duration ME/CFS patients and depleted immune systems in longer- duration patients.

Unutmaz is now trying to identify which bacteria are tweaking ME/CFS patients’ MAIT T-cells so much as to possibly burn them out. If he’s successful, he may have found a target that could quiet down a possibly overworked and burnt-out immune system and allow it to rejuvenate.

I liked this from Keller too. Almost enough to make me want to get a two CPET

Keller stated that people with lung disease, heart disease or sedentary controls are able to replicate their energy production to a surprisingly precise degree (differing by 1-7%) on the second day of a two-day maximal exercise test. Many people with ME/CFS cannot – something happens to them during or after exercise to disturb one of the most fundamental biological processes of all: their ability to turn oxygen into energy goes down, sometimes quite severely. Hanson reported that a former marathon runner’s ability to produce energy went down a staggering 44% after one maximal exercise test.

 

[bertiedog]

I'm interested in Unutmaz and his T-Cell work that finds a link to the gut certainly seems like it could be a missing link for us.

This seems to tie in with the description the Scientist was giving in her interview in the BBC Radio 4 recording today of Life Scientific which I posted earlier.

I cannot believe that this won't pan out as to be a major issue for many of us with ME.

Pam

 

[msf]

There's a whole thread and pilot study on it, just Google it. DCA stands for dichloroacetate. If you want to know how it might work, I wrote a blog about how I think ME works.

Both part of @Cort's montreal write-up are worth a read.

I'm interested in Unutmaz and his T-Cell work that finds a link to the gut certainly seems like it could be a missing link for us.



I liked this from Keller too. Almost enough to make me want to get a two CPET

Yeah, the t cell stuff is really interesting, and kdm et all have reported a t cell independent pathway that is altered in me patients too. The word activated suggests that the MAIT cells are also ramping up glycolysis, hence the effectiveness (I believe) of dca in ramping down the immune response.

 

[msf]

Oops, didn't mean to quote myself.