The News From the London Invest in ME Conference

[Cort]

Check out what happened in the 10th Invest in ME Conference. I'll be riffing on tweets emanating from the Conference. If you like the updates please post using your Twitter or Facebook accounts and our handy social media bar.

08.55 Dr. Ian Gibson Conference Opens
09.05 Professor Ian Charles (Keynote Speech) Solving ME: What a Research Park Has to Offer in Resolving a Chronic Disease
09.30 Professor Mady Hornig Markers of Immunity and Metabolism in ME/CFS
10.00 Professor Jonas Bergquist Proteomics in ME/CFS
10.25 Refreshments Break
10.50 Dr. Luis Nacul Incidence and Prevalence of ME
11.15 Dr. Amolak Bansal Diagnosis and Differential Diagnosis: Combining clinic and research
11.45 Professor Sonya Marshall-Gradisnik, Dr Don Staines (To be confirmed) Update from National Centre for Neuroimmunology and Emerging Diseases – NCNED
12.15 IiME Projects Student Researchers: The Next Generation
12.40 Lunch
13.40 Dr. Jo Cambridge B-cell biology and ME/CFS
14.05 Dr. Neil Harrison Immune-Brain Communication and Relationship to Inflammation
14.30 Dr. John Chia ME and Chronic Enterovirus Infection: An Update on pathogenesis.
14.55 Dr. Claire Hutchinson Biomarkers for ME: Visual Processing and ME/CFS
15.20 Refreshments break
15.50 Professor Betsy Keller Molecular markers before/after exercise /Activity guidelines to avoid symptom flares
16.15 Dr. Oystein Fluge, Professor Olav Mella Multi-centre Rituximab Clinical Trial for ME/CFS
17.10 Plenary Will ME Be Treatable/Cured?
17.30 Dr. Ian Gibson Adjourn

 

[Cort]

The information is taken from tweets posted on the Phoenix Rising twitter account.

Mady Hornig Talk: Markers of Immunity and Metabolism in ME/CFS

The Center for Infection and Immunity appears to be planning a new Microbiome and Immunology study. Hornig noted that group has found reduced pro-inflammatory cytokine production in longer term patients in both their blood an spinal fluid studies. She also presented some new findings - which are embargoed for the time being.

Dr Jonas Berquist: Markers of Immunity and Metabolism in ME/CFS

Dr. Berquist is engaged in a spinal fluid proteomics study. Proteins are where the rubber meets the road in the body. They - not the genes- do the work in the body. The genes purpose is to create proteins. Proteomics - the study of the proteins in the body - then has much promise. It's also very expensive and very complicated.

This appears to be the third ME/CFS spinal proteome study Berquist has been involved in. A 2011 study was able to differentiate ME/CFS patients from Lyme disease patients and from healthy controls. At that time, Schutzer, the leader of the study said

"The next steps will be to narrow down this large group of proteins by looking for a handful of them at a time in patient spinal fluid. In addition, if a protein pathway is found to influence either disease, scientists could then develop treatments to target that particular pathway."

"Newer techniques that are being developed by the team will allow researchers to dig even deeper and get more information for these and other neurologic diseases,"

This study is apparently the result of that work. They found evidence of low grade inflammation and problems with "axonal guidance" in ME/CFS. The low grade inflammation fits - that's exactly what Jarred Younger is looking for and what the Japanese study found.

They are not looking for "high-grade" inflammation - other studies would have picked up "high-grade" inflammation. They're looking for low grade inflammation. Tools are just being developed that can pick up low-grade inflammation in the brain.

At least three studies looking for low-levels of inflammation in the brain using imaging techniques are underway: the Japanese reprise of their study, Jarred Younger's study using an entirely different technique at the University of Alabama, and Andrew Lloyd's study in Australia. Lloyd's study won't be done for at least another year.

Berquists finding of low-grade inflammation in the proteins off the spinal cord fluid can only bolster brain imaging findings of the same. The fact that this difficult research is continuing to get funded is in itself a good sign.

(Other information was embargoed again. I've never seen so much "embargoed" information. No information is embargoed at the IACFS/ME Conference and abstracts/etc. are freely available at other conferences.)

 

[Who Me?]

I'm not on Twitter. Could someone post here anything that comes through? Keep this threaded dedicated for tweets?

 

[Cort]

Dr Amolak Bansal: Diagnosis and Differential Diagnosis: Combining clinic and research

Abnormal Pupil Activity Suggests Autonomic Neuropathy - Some real news. Banai reports people with ME/CFS have abnormal pupil reflexes -- an abnormality that is usually only found in people with autonomic neuropathy. The opening of the iris is controlled by the sympathetic nervous system whereas the closing of the irs is controlled by the parasympathetic nervous system. People with diabetes often have reduced pupil reflexes due to damage to their autonomic nerves.

One wonders if reduced pupil reflexes could be partially for the sensitivity to light found. If the parasympathetic nervous system is not closing the iris quickly enough in response to light it might produce pain.

That's a fascinating finding given Dr. Martinez-Levins recently finding of high rates of small fiber neuropathy in the corneas of the eyes of people with fibromyalgia. The cornea problems shouldn't affect the sight but abnormal pupillary reflexes sounds like they could.

People with FM appear to have degradation of their sensory and, in some cases, their autonomic nerves. My understanding is that in the skin and probably elsewhere these two types of nerves are closely intertwined. Could people with ME/CFS have more autonomic nerve fiber problems (and less sensory nerve problems) than people with FM?

According to Wikipedia abnormal pupillary reflexes provides a useful diagnostic tool for testing the integrity of the sensory and motor functions of the eye.[1]

Clinical

Bansai reports that 20% of people with ME/CFS also have joint hypermobility and 80% have increased respiratory rates! That would be no surprise to Dr. Natelson and his hyperventilation results and may fit in well with Dr. Newton's findings that pH problems in the muscles trigger changes in the brain. It may fit with the sympathetic nervous system hyperactivity found. In any case, it's more evidence of some sort of overactivation and we're going to see more of that later in the conference.

ME/CFS Mimics

Disorders that mimic ME/CFS: EDS-3, hypothyroidism, Addison's disease, Sjorgen's, gluten sensitivity, sleep disorders, cardiac dysfunction, Parkinson's, TMD, persistent anxiety and depression.

Glad he got Sjogren's in there but I would addd MS, polymyalgia rheumatica, hyperparathyroidism and pyruloria.

 

[Cort]

I'm not on Twitter. Could someone post here anything that comes through? Keep this threaded dedicated for tweets?

Everything I'm reporting is coming from ME/CFS patients twittering away....

 

[Cort]

Dr. Luis Nacul: Incidence and Prevalence of ME

Nacul believes the puzzle pieces are coming together. He believes SEID is not specific enough. That comment immediately erodes my confidence in him since studies have shown that more specific diagnostic screens end up creating a patient group with extremely high levels of mood disorders. Besides, Jason has shown that a very simple screen - if it uses the right symptoms - is quite specific for ME/CFS......

He may be aiming at subsets though. You definitely need more specific definitions to identify the subsets in this disorder. Jason takes care of that by using a broad definition and then breaking it up.

CBT/GET - notes Cochrane reports provide little strong endorsement from either....

Not else much here...Oxford definition must go.....Nacul appears to have just gone over much of what we already know. Time to move on!

 

[Cort]

Dr Don Staines/Sonya Marshall Gradisnuk : Update from National Centre for Neuroimmunology and Emerging Diseases – NCNED

We've covered about half of these findings in a recent blog. The NCNED is examining genetic variability in a variety central nervous system and immune genes. They appear to have hit some paydirt: they're finding concentrations of unusual forms of a few genes in ME/CFS patients.

Those genes are:

• ACTH AChR SNP's -- located in the GI tract, regulate insulin secretion, involved in arousal and sleep and fatigue, pain, memory
• TRPC4 -- responsible for vasomotor function and smooth muscle function, memory and attention, and motor cont
• TRPM3 is located in the central nervous system -- associated with pain in the absence of tissue damage, also a thermoregulatory sensor.
• TRPA1 -- has a role in the regulation of neuropeptides, as well as pain and inflammation

Vasomotor and smooth muscle (blood vessels), pain without tissue damage, arousal (or the lack of it), metabolism - these are all implicated in ME/CFS. The NCNED chose their genes well.

Another bit of good news is that the NCNED is finding highly concentrated genetic problems. That suggests they're on the right track and may be uncovering genetic variations that strongly predispose people to coming down with ME/CFS.

It's good as well that some of the receptors associated with these genes have shown up in the Light's studies.

 

[Cort]

Dr. Jo Cambridge: B-cell biology and ME/CFS - No Smoking Guns Yet

B-cells have been a tough nut to crack in ME/CFS. The evidence from the Rituximab trials suggests they are involved but studies examining them have, thus far, come up with little. Here Dr. Jo Cambridge reports on a preliminary trial being conducted designed to help UK researchers figure out who benefits from Rituximab and how it is having the effects it does.

Rituximab is a B-cell depleter and it affects cytokine production. B and T cells are intertwined. B-cells present an antigen (small bit of a virus) to a T-cell. T-cells then produced cytokines that help B-cells react.

A recent study suggested some B-cell differences are present between healthy controls and ME/CFS patients but it doesn't appear that there's anything conclusive - no smoking guns yet so to speak.

 

[Cort]

Dr Neil Harrison: Immune-Brain Communication and Relationship to Inflammation

Harrison talks about "sickness behavior" and how inflammation can cause fatigue, pain, cognitive problems, etc. The news that inflammation is present in the body is usually transmitted to the brain via the vagus nerve. The effect inflammation in the body can have on the brain clear when people given a cytokine - interferon - for the treatment of hepatitis often immediately became very fatigued. Studies indicated that their brain "microstructure" had changed within four hours. That finding made it clear that inflammation can cause a wide variety of pain and fatigue symptoms.

(Interestingly not all of the people getting interferon became fatigued. Why some people don't is a major question the answer of which could have significant implications for ME/CFS. Some researchers are - slowly - looking at that. If they can find the factor that turns off the fatigue, though, they might have an answer for ME/CFS. The reason for that is that the brains of hepatitis patients treated with interferon look very much like ME/CFS patients).

Several researchers think the brains of ME/CFS patients have become so sensitized to inflammation that only slight increases are needed to produce fatigue and/or pain.

Harrison asserted that the insula in the brain may be a major factor in the production of fatigue and pain in ME/CFS and FM. It affects both interoception (one's sense of how one's body is doing) and autonomic nervous system function. It's implicated in pain production in FM.

This was another overview talk - a bit disappointing! - one would rather have fresh findings at a conference like this but the vagus nerve connection, the interferon information and the insula showing up in both FM and ME/CFS is definitely intriguing.

 

[Cort]

Dr. John Chia: ME and Chronic Enterovirus Infection: An Update on pathogenesis.

Chia stated that most doctors do not know how a) to recognize what an enterovirus infection looks like or b) that they can cause chronic infections. Even gastrointestinal specialists often don't recognize enteroviruses can cause gut problems. (Chia is swimming in lonely waters!)

Chia is confident though that if you're having gut symptoms you should be able to find an enteroviral infection in the gut. He believes most viral replication takes place in the gut.

He believes the enteroviral infections in ME/CFS travel from the guts of ME/CFS patients into their brain via the vagus nerve. This was apparently his promised "big finding" but if he presented evidence for that it wasn't picked up by the tweeters. My guess is that he must have some evidence for that but it's not clear what.

The CDC is testing his samples for enteroviral infections but no information was apparently presented on the outcome of those tests.

I will try to find out more about Chia and his update on pathogenesis.

 

[Cort]

Dr Claire Hutchinson - Biomarkers for ME: Visual Processing and ME/CFS.

"The eyes are the window to your....err nervous system" (not William Shakespeare)​

Finally a major finding. Dr. Hutchinson reports finding a variety of visual problems in ME/CFS: problems focusing, hypersensitivity to light, itchy dry eyes, eye pain, loss of depth perception, problems tracking objects. The more frequent the symptoms, the greater the severity. (A stress/visual glare test can pick these problems up. )

These aren't just eye problems - they're brain problems. Similar problems are found in disorders of cortical hyperexcitability such as epilepsy, stroke and MS. (If migraine wasn't mentioned it probably should have been. Cortical hyperexcitability is found in migraine as well. The rates of migraine in FM and ME/CFS may be pretty staggering (55% in FM) and visual hypersensitivity is a key factor in migraine. It may, in fact, be the most common comorbid disorder in FM. We are probably going to be hearing a lot more about the connections between migraine and ME/CFS and FM over the next couple of years. )

Cortical hyperexcitability could be caused by problems with GABA production or other factors. It may reflect an inability of the brains inhibitory processes from kicking in to slow the brain down. Interestingly, vagus nerve stimulation is one of the treatments used to reduce cortical hyperexcitability. Check out "Reborn..." - recent blog on vagus nerve stimulation.

Patients were slower at finding targets than controls and the more distractions present the worst the ME/CFS patients did. This is reminiscent of the brain finding indicating that ME/CFS patients brains have trouble disengaging themselves from background sounds, images etc. to focus on the task at hand.

Interestingly, ME/CFS patients visual processing speed was OK, but they needed an item to appear for longer before they picked it up - presumably because their brain was engaged in assessing other stimuli.

Dr. Hutchinson is leading projects on reading behaviour, vision-related quality of life, and opthamalic correlates of ME/CFS.

Who knew eye research would end up being so interesting? The eyes are indeed the windows to something in ME/CFS.

The eyes are suddenly getting quite a bit of research. Just recently we have evidence of small fiber neuropathy in the cornea of FM patients eyes, autonomic neuropathy in ME/CFS patients eyes and now problems with tracking, visual hypersensitivity, etc. in ME/CFS patients...

 

[justME]

scary stuff, the replacement in case Rituximab doesn't do the trick but at least they're tapping spines, speakingofscarystuff

and SO frustrating, stealthviruses (the adapted and milder, so they can get into the brain, versions of regular ones) are fairly easy to get rid of

 

[Cort]

Professor Betsy Keller: Molecular markers before/after exercise /Activity guidelines to avoid symptom flares

Spinal alignment is key for good function and energy conservation. Dr. Keller​

No news on molecular markers but a guide to realigning the spine instead. That's probably a darn good idea given reports from Dr. Lapp that people with ME/CFS often have hunched over shoulders and pinched in chests that make it difficult to breath deeply.

Five Steps to Realign the Spine

1. Contract pelvic floor. eg for women -- eg kegel exercises
2. Draw-in or Brace ('suck belly-button into spine.) to stabilize pelvis
3. Raise ribcage - pretend ribcage is an umbrella
4. Back extension -- lie on floor in flying Superman pose - slide shoulder blades together or shoulders back and down.
5. Retract chin is the last step to aligning spine.

Keller recommends physio balls, yoga to strengthen the core.

 

[Cort]

Dr. Oystein Fluge, Professor Olav Mella - Multi-centre Rituximab Clinical Trial for ME/CFS

The big Rituximab study will finish up in 2017 - just a year and a half away...(Did I really say JUST a year and a half away?). It's a large study and we'll pretty much know about how effective Rituximab is in ME/CFS after that. You have to ask yourself how often we have a trial big enough to say that in ME/CFS.

Blood Banking!
They'll be taking blood samples regularly and putting them in a biobank. (One wonders how many liters of ME/CFS blood are now stored in biobanks? From almost nothing five or so years ago we now have biobanks - some of them quite large - at Simmaron Research, The Solve ME/CFS Initiative, Chronic Fatigue Initiative, Stanford, the NIH, the CDC, Invest in ME, the Institute for Neuroimmne Studies and I'm sure I'm forgetting some.... That's great progress in this field.

Activity Monitoring
Finally someone is activity monitoring! That takes guts in this disease but it also shows confidence. They'll be measuring activity using armbands.

Recruitment Finishing Up
Two of the centres have finished recruitment and two more will finish up by the end of summer.

Some Will Respond!

There is no doubt but that some will respond. The question is how many. A big question given Rituximab's cost is whether Fluge and Mella or Invest in ME or someone else is going to be able to end up predicting who will - and thus get them access to insurance coverage.

Cooperation on All Fronts

The study has been good for ME/CFS in Norway. The hospitals are cooperating. Fluge/Mella got government, private and charity support. The charity there movement mountains to get this study funded. It's amazing to see this big, oh so important study being funded by this small country (while the U.S. sits on its hands.) Kudo's to the Norwegians!

• Learn more about the study in: The Biggest Chronic Fatigue Syndrome Treatment Trial Begins: Fluge/Mella On Rituximab

New Drug Possibility

They may use a powerful drug called cyclophosphamide for those who can't tolerate Rituximab. They got good results from a very small preliminary study and if I got the tweets right bumped the trial up to 40 patients in March of this year. (This would never happen in the US....)

Cyclophosphamide is used to is used to treat cancers, autoimmune disorders, and AL amyloidosis. It's an important treatment for life-threatening autoimmune diseases such as lupus where other drugs have been ineffective. Cyclophosphamide is also used to treat minimal change disease,[13] severe rheumatoid arthritis,[14] granulomatosis with polyangiitis[15] and multiple sclerosis.[16 .(From Wikipedia)

It's an important drug - it's actually listed as one of the key drugs medical systems should have - but it can have severe side effects, particularly when given at high doses. They include (hold your breath) acute myeloid leukemia, bladder cancer, hemorrhagic cystitis, and permanent infertility. (I imagine Fluge/Mella are using low doses.)

Fluge and Mella keep moving forward and trying new things. They're an impressive team and they're clearly committed to finding answers. Their background is cancer is bringing new treatments to the fore. Expect some more papers out in the not too distant future.

 

[Cort]

scary stuff, the replacement in case Rituximab doesn't do the trick but at least they're tapping spines, speaking of scary stuff

They're definitely going for it....

 

[AnIrishGuy]

(I've never seen so much "embargoed" information. No information is embargoed at the IACFS/ME Conference nor and abstracts/etc. are freely available at other conferences.)

I'm not sure the Invest in ME conference has official status.
Researchers have to submit their work for acceptance at a conference like the IACFS/ME. The abstracts and posters are a bit like getting published. It's not the same with the Invest in ME conference as I see it.

 

[AnIrishGuy]

Dr Amolak Bansal: Diagnosis and Differential Diagnosis: Combining clinic and research

Abnormal Pupil Activity Suggests Autonomic Neuropathy - Some real news. Banai reports people with ME/CFS have abnormal pupil reflexes -- an abnormality that is usually only found in people with autonomic neuropathy. That's a fascinating finding given Dr. Martinez-Levins recently finding of high rates of small fiber neuropathy in the corneas of the eyes of people with fibromyalgia. The cornea problems shouldn't affect the sight but abnormal pupillary reflexes sounds like they could.

A UK researcher, Ian James, found abnormal pupil responses 15 years ago. Unfortunately he passed away before he was able to publish his results:
http://www.dailymail.co.uk/health/article-641/Eye-test-hope-ME-sufferers.html

 

[Who Me?]

Dr. John Chia: ME and Chronic Enterovirus Infection: An

No information was apparently presented on the tests the CDC is doing on his samples.

I will try to find out more about Chia and his update on pathogenesis.

So no great revelation about enteroviruses? Like an easy way to test?

 

[Cort]

I'm not sure the Invest in ME conference has official status.
Researchers have to submit their work for acceptance at a conference like the IACFS/ME. The abstracts and posters are a bit like getting published. It's not the same with the Invest in ME conference as I see it.

You may be right. I don't know why it would be different for them than IACFS/ME but what the heck do I know? The DVD with all the presentations is going to be out in a month or so...the cat will be out of the bag then.

 

[Cort]

A UK researcher, Ian James, found abnormal pupil responses 15 years ago. Unfortunately he passed away before he was able to publish his results:
http://www.dailymail.co.uk/health/article-641/Eye-test-hope-ME-sufferers.html

Isn't that amazing. Good find IrishGuy - never heard of that before. It looks our new researcher is going to be busy for awhile...