A Great Addition to the ME/CFS Field

Dr. Maureen Hanson has been all over the place in chronic fatigue syndrome (ME/CFS) lately.
Hailing from Duke and Harvard and now at Cornell she has quite a pedigree. With a family member with chronic fatigue syndrome (ME/CFS), she also has a personal stake in this disease, and has penned several editorials supporting ME/CFS research. Her "Be Aware and Beware" Huffington Post blog and her Congressional Hill post "When Hoofbeats are Zebras" showed that she's not afraid to leave the laboratory and get out and advocate. At every opportunity she makes it very clear that ME/CFS is a real disorder. Her last gut study went viral and was picked up by over 50 media outlets.

She recently spoke at the Invest in ME Conference, and at the Simmaron Patient event, and is on the scientific board of the Simmaron Research Foundation.

As and added bonus she appears to be very good at getting NIH grants. She first popped up in ME/CFS with a grant to study XMRV in 2011. Since 2011 she's gotten three R21 grants on ME/CFS, and is a collaborator on a big RO1 immune functioning grant with Fabian Campagne at Cornell. She's also being funded by the Hitchens Foundation's Chronic Fatigue Initiative. She seems to have a talent for taking on interesting studies. She's definitely someone to keep an eye on.

Metabolomics

Now she's moving into metabolomics. In the Solve ME/CFS webinar this week Hanson revealed that a small metabolomics study she pieced together using donations had replicated Naviaux's core finding - that ME/CFS is hypometabolic disorder.

Her study was smaller than Naviaux's: compare the 80 or so patients/controls and 612 metabolites measured in his study to the 32 patients/controls and 361 metabolites in the Hanson pilot study. All the participants n her study were also female and all came from an ME/CFS expert, Dr. Susan Levine, who has been collaborating heavily with Dr. Hanson.

Naviaux noted that the field is moving so quickly that it lacks standardization and this study showed it. The Hanson team used a different kind of mass spectrometer, and handled the samples differently. In fact, the way Hanson was talking, it sounded like everything was done differently in the Hanson study.

Nevertheless, Hanson's core findings were strikingly similar to Naviaux's. She found an almost across the board reduction in metabolite levels; fully eighty-eight percent of the metabolites in the ME/CFS patients were reduced (compared to 84% in Naviaux's study.)

Some similar pathways (phospholipids, purines, proline, fatty acid metabolism) showed up and others did not. The dramatic sphingolipid reductions Naviaux found, for instance, did not show up in the Hanson study, and Hanson found several pathways that did not show up in the Naviaux study.

Hanson suggested that the completely different methods used as well as the different geographic region the patients hailed from could explain the differences found. Whatever the differences found, the core finding of a distinct hypometabolism in chronic fatigue syndrome (ME/CFS) clearly excited Hanson and she stated:
"The similarities are very promising for metabolomics to give some very useful information about ME/CFS"
Click to expand...
Hanson's metabolomic money is gone, but she's applying for an NIH grant. Scoring a big ROI grant - say $3,000,000 over several years - would, of course, be a major step forward for metabolomic research in ME/CFS.

How to Fit Many Symptoms into One Core Pathology ...

With the Chronic Fatigue Initiative's help, Hanson has also been studying mitochondrial genetics. Naviaux has stated that people with ME/CFCS do not have a genetic mitochondrial disease, and Hanson's results backed that assertion up; in fact, none of the almost 200 patients tested had anything suggesting an inherited mitochondrial condition. She did, however, find evidence - as Ron Davis has suggested - that genetic polymorphisms could be producing different symptoms in different ME/CFS patients.

Maureen Hanson's Solve ME/CFS Initiative Webinar

One altered mitochondrial DNA gene, for instance, appeared to be associated with gut symptoms; another was correlated with chemical sensitivity - a problem that gets almost no research attention - but can be terribly impactful. (Dr. Naviaux believes, interestingly enough, that low energy states lend themselves to hypersensitivity reactions. )Hanson's study suggested genetic differences in the mitochondria could result in widely varying symptoms in ME/CFS. She noted though, that much, much larger studies are needed to validate her findings.

Hanson is not by any means done with the mitochondria; she is also examining the mitochondrial functioning of NK, T and B cells. The poor functioning of NK cells is one of the most consistently found immune abnormalities in ME/CFS, but problems with T-cell functioning have also been found, and reports of poorly functioning B-cells have shown up as well.

Could the immune problems in ME/CFS be caused by a hypo-metabolic or under-energized immune system? Hanson will use an Agilent device to determine if problems with glyoclysis - the energy pathway that releases ATP and ATP through the conversion of glucose - are sending immune cells into a somnolent state.

Hanson then went on talk about her recent gut findings which included a reduction (another reduction) in diversity and abundance of microbial species in ME/CFS. She also suggested that the reduction in microbial diversity seen in an ill twin might be associated with that twins reduced aerobic capacity.

A New Chronic Fatigue Syndrome (ME/CFS) Center

In some very good news Hanson announced that the Dean at Cornell has allowed Dr. Hanson to create a new ME/CFS research center called the "Center for Enervating NeuroImmune Disease" (CEND). (Enervating means feeling weak and lacking in energy). The Center will collaborate with Betsy Keller at Ithaca College. It contains three researchers, involves eight labs which have or are applying for an ME/CFS grant, and is working with no less than five physicians - and Hanson hopes it will grow significantly.

The fact that Hanson felt it was time to create a formal center for ME/CFS at Cornell, plus her ability to hit the ground running with a strong staff is very encouraging particularly at Cornell - which has a top ranked Medical School. The new Center will surely be a strong candidate for the projected NIH research consortium.

Maureen Hanson is clearly the kind of researcher we've been looking for and hope to get more of. She's very committed, she can get grants, she's daring enough to start an ME/CFS research center and she clearly works well with others.

Some ME/CFS Metabolomic / Metabolic Studies Coming Up

The Naviaux study really caught our attention but a surprising number of other groups are doing metabolomics/metabolic/mitochondrial studies. McGregor in Australia, for instance, has been studying metabolism/metabolomics in ME/CFS for years. Here are some metabolomic / mitochondrial studies underway.
o    Hanson's small ME/CFS metabolic study (under review now).
o    The Naviaux/Ron Davis OMF funded expansion of Naviaux's recent study
o    Naviaux's studycomparing the metabolome of ME/CFS patients and other diseases
o    Hanson's NK, T and B cell energy production study
o    The Lipkin/Hornig study tying metabolomics results in the blood to their gut findings.
o    The Bateman Horne Center/Watanabe Japanese metabolomics study. In what is clearly a Suzanne Vernon study, the Watanabe study, a Michael Hougton Canadian Cytokine Study, and Alan Light's Autoantibody study will all use the same 100 patients samples - thus allowing them potentially to merge their findings.....
o    Nath's metabolic chamber study in the Intramural study
o    Several studies from Armstrong and McGregor in Australia
o    The SolveME/CFS in house mitochondrial study (more on that later.)
The Bateman-Horne Study
Depression - Sometimes a Metabolic Disorder?

ME/CFS might not be the only disease which may get turned around by metabolomics. Let's take a quick look at a metabolomic study that could turn the medical profession's conception of depression - a disease that's often been confused with ME/CFS by doctors - upside down.

The potential breakthrough started, as many breakthroughs do, with one patient. As reported in the Pittsburg Post-Gazette, frustrated doctors who had run out of options with a treatment resistant young man with suicidal depression, turned to a biochemical geneticist for help.
The geneticist suggested doing a metabolic analysis of the young mans cerebral spinal fluid. That analysis turned the his life around. After finding that he had deficient levels of a protein called tetrahydrobiopterin, or BH4, they began treating him with a substance called sapropterin. He was able to recover, return to school and is now working in his chosen field.

After getting the same results in five other treatment resistant depressed patients, the group began a larger study looking at hundreds of metabolites in the spinal fluid of 33 patients. About two thirds of them displayed significant metabolic abnormalities; of those more than half (12/21) had the same cerebral folate deficiency found in the young man. All showed improvements including reductions in suicidal thoughts on a high dose regimen of folinic acid.

For some young people on the protocol the improvements have been dramatic. The parents of one 13 year stated that within a month of taking the folinic acid, “we felt like we had our Ben back."

This isn't to say that all the patients had that kind of result, but it does indicate the power of this technology to uncover new insights that can lead to dramatic improvements even in seemingly intractable diseases like treatment resistant depression (and who knows...perhaps ME/CFS.)

What would, one wonders, a metabolomic analysis of ME/CFS patients cerebral spinal fluid find?
 
Bottom of Form

 

The Economist
Chronic-fatigue syndrome
A new test may diagnose a mysterious illness, and also help to explain it
Sep 3rd 2016 | From the print edition
·          
CHRONIC-FATIGUE SYNDROME, or CFS, which afflicts over 1m people in America and 250,000 in Britain, is certainly chronic and surely fatiguing. But is it truly a syndrome, a set of symptoms reliably associated together and thought to have a single underlying cause—in other words, a definable disease?
CFS’s symptoms—debilitating exhaustion often accompanied by pain, muscle weakness, sleep problems, “brain fog” and depression—overlap with those of other conditions. These include fibromyalgia (itself the subject of existential doubt), clinical depression, insomnia and other sleep disorders, anaemia and diabetes. These overlaps lead some to be sceptical about CFS’s syndromic nature. They also mean many people with CFS spend years on an expensive “diagnostic odyssey” to try to find out what is going on.
Scepticism about CFS’s true nature is reinforced by the number of causes proposed for it. Viruses, bacteria, fungi and other types of parasite have all had the finger pointed at them. So have various chemicals and physical trauma. Evidence that CFS truly does deserve all three elements of its name has accumulated over the years but a definitive diagnostic test has remained elusive. Until, perhaps, now. For in this week’s Proceedings of the National Academy of Sciences Robert Naviaux of the University of California, San Diego, and his colleagues published evidence that the metabolisms of those diagnosed with CFS are all changing in the same way. Their data suggest it is this cellular response to CFS-triggering traumas, and not the way the response is set in motion, which should define the illness. They also show that this response produces a chemical signal that might be used for diagnosis.

Dr Naviaux and his team collected and analysed blood samples from 45 people who had been diagnosed with CFS, and also from 39 controls who were free of any CFS-related symptom. They then trawled through those samples looking at the levels of 612 specific chemicals, known as metabolites, which are produced during the day-to-day operations of living cells.
These metabolite profiles, they found, differed clearly and systematically between the patients and the controls. Some 20 metabolic pathways were affected, with most patients having about 40 specific abnormalities. The biggest differences were in levels of sphingolipids, which are involved in intercellular communication, though other molecules played a role as well. These differences should give clues as to what is happening at a cellular level during CFS. More immediately, a handful of the abnormalities—eight in men and 13 in women—were enough, collectively, to diagnose with greater than 90% accuracy who had the disease.
That is a good start. If this discovery is to lead to a reliable test for CFS, though, Dr Naviaux’s experiment will have to be repeated to compare those diagnosed as having CFS with those who are not so diagnosed yet display some of its symptoms. The answer should soon become apparent, for he is already applying his method to people who have depression, autism, traumatic brain injury and post-traumatic-stress disorder.
One crucial question that needs an answer if CFS is to be understood better is: what cellular changes are these metabolic abnormalities bringing about? Here, Dr Naviaux has already made an intriguing and slightly disturbing discovery. Similar metabolite profiles to those seen in CFS are characteristic of a state known as “dauer” that occurs in one of biology’s most-studied animals, a soil-dwelling threadworm called C. elegans (pictured). In dauer, which is reminiscent of hibernation in larger creatures, the worm puts its development on hold and enters a state of suspended animation in response to threats such as reduced food, water or oxygen levels. It can survive this way for months, though the lifespan of an active worm is mere weeks.
It may be a coincidence, but six of the diagnostic metabolites whose levels are low in CFS are also low in dauer. If it is not a coincidence, though, that suggests a biochemical overlap between the two conditions. If this were true, it could be of great value both in understanding CFS’s underlying biology and (because C. elegans is so well examined and easy to study) in experimenting with potential treatments.
From the print edition: Science and technology
 

​What Clinicians Should Know About the New Lyme Species
Paul G. Auwaerter, MD
 March 01, 2016 – Medscape Family Medicine
Hello. This is Paul Auwaerter with Medscape Infectious Diseases, from the Division of Infectious Diseases at Johns Hopkins. Tickborne infections continue to surprise us. Lyme disease historically has been the top vector-borne illness in North America, with 20,000-36,000 reported cases annually, although estimates suggest that the actual number of cases occurring in the United States annually might be upwards of 300,000.[1]
Other members of the Borrelia genus cause disease in the United States. Perhaps the oldest, known for many decades, have been the agents of relapsing fever—either louse-borne (which is fairly rare in this country) or, more commonly, tickborne. Tickborne relapsing fever is spread by soft ticks that like to bite at night, especially campers in sleeping bags, and often in elevated climates of 2000-7000 feet above sea level in the western United States.[2]
But two more recent borrelial species deserve some attention for anyone who treats patients who might have acquired a tickborne infection. The first is B miyamotoi.[3] This was first described in Russia a few years ago and was initially thought to cause a relapsing fever-like illness, but in the United States it was first described as causing a meningoencephalitis. B miyamotoi seems to be transmitted by the same deer tick that transmits Lyme disease, and commercial assays for testing for it aren't yet widely available. However, this infection can be severe enough to cause hospitalization with a sepsis-like presentation. More commonly, it is associated with a febrile illness and can be confused with atypical Lyme disease (without a rash), ehrlichiosis, or anaplasmosis.
However, the newest kid on the block was just described by groups at the Mayo Clinic and the Centers for Disease Control and Prevention.[4] The Mayo Clinic has been a reference lab for many tests throughout the United States. They have drawn samples from around the country and found six samples using polymerase chain reaction (PCR) testing for suspected Lyme disease that had atypical melting curves. Upon further genetic analysis, they found that this was a new species, which they have given the candidate name of B mayonii in recognition of where the work was done.
Of interest, the six patients were all from the upper Midwest—Minnesota or Wisconsin. All were ill with fever and rash. One was described as having an erythema migrans rash, others had diffuse maculopapular rashes. There is a suggestion of neurologic syndromes. One patient had arthritis and two others were ill enough to be admitted to the hospital.
Somewhat different from Lyme disease, however, is that some of these patients had very high spirochete loads in their blood. This skews more to what you might find in traditional relapsing fever.
Now, what does this mean? The authors suggest that this is a newly emerging borrelial infection because it hadn't been described in more than 90,000 samples from different regions that they had analyzed earlier, so they think it could just be found in the upper Midwest. Obviously, however, this is very much in the earliest stages.
This situation seems very similar to that in Europe, where B burgdorferi sensu stricto (what we have had here in the United States) accounts only for a small proportion of Lyme borreliosis. B garinii and B afzelii account for far more cases. Several borrelial species account for infections there. We are no longer limited to only one now that B mayonii is a separate entity.
There are no specific diagnostic tests yet. It is uncertain whether a B burgdorferi PCR would pick this up routinely. The Lyme C6 antibody, which is US Food and Drug Administration approved, at least detected the infection in all four patients. Less successful was the traditional two-tier immunoblot testing, although the IgM Western blot was positive in three out of three people tested. The IgG assay was far less successful.
Whether these patients need different treatment is unclear. They were treated the way that we would treat any tickborne infection. That is the right response at the current time.
Stay tuned, because we might uncover more tickborne infections with advanced molecular technologies. Clinicians should pay attention to what they think might be Lyme disease, ehrlichiosis, or anaplasmosis, which may indeed represent some of these alternative infections

 
 
From: Wall St JournalPatients, Scientists Fight Over Research-Data AccessSome scientists balk at disclosing details in study of chronic fatigue syndromeAmy Dockser Marcus
March 7, 2016 6:51 p.m. ET
A controversy surrounding a study of chronic fatigue syndrome is prompting some scientists to push back against demands that they make medical research data more widely available to other researchers and patients.
Data from clinical trials and other studies are increasingly open to public scrutiny. Proponents of open access say it can aid other scientists seeking to check research conclusions, and patient groups say it can help determine how useful potential new treatment options may be. The National Institutes of Health requires researchers it funds to make data available to other scientists and the public. And some medical journals have begun making open release of data a condition for publication.
But some scientists are concerned that research data in the wrong hands may be misused or misinterpreted. They also fear they may face harassment from other scientists or patients who disagree with the findings.
The debate recently boiled over regarding the long-running study in the United Kingdom of ME/CFS, a debilitating and poorly understood condition also known as myalgic encephalomyelitis or chronic fatigue syndrome. The study found that either a program of gradually increasing exercise, or cognitive behavioral therapy, led to modest improvements in patients’ fatigue and physical functioning compared with standard medical treatment, which consists mainly of educating patients about the condition and treating symptoms such as pain. The study, which is commonly known as Pace and involved 640 chronic fatigue patients, was first published in the journal the Lancet in 2011.
Some patients and other scientists have doubted the study’s conclusions. “These theories presume and insist that patients are not medically sick but simply suffering from dysfunctional cognitions that need to be changed,” said David Tuller, a lecturer in public health and journalism at the University of California, Berkeley. Dr. Tuller wrote an extensive analysis describing methodological problems with the Pace study that ran in October in “Virology Blog,” a widely read scientific blog.
On Monday, 43 scientists and clinicians sent a letter to the Lancet asking it to seek an independent reanalysis of the Pace study data. A petition disputing the trial results, and signed by 11,000 patients, caregivers and doctors, was submitted to the university, medical journals and posted online last week asking the researchers to release the data. And in October, the Information Commissioner’s Office, a U.K. independent authority that rules on public access to information, said Queen Mary University of London, which ran the Pace trial, must turn over research data to a patient who requested it; an appeal by the university will be heard next month.
Controversy has long surrounded ME/CFS, including how to define it and treat it. The National Institutes of Health in October said it was going to strengthen efforts to study the condition and find better prevention and treatment approaches. The Institute of Medicine found in a 2015 report about ME/CFS that exertion can make patients’ symptoms worse.
Queen Mary University declined to make the Pace investigators available for an interview. In a statement it said: “We have supplied requested, anonymized data to independent scientists, as part of the normal research collaboration.” It added it is also concerned for “the rights and welfare of trial participants.” The university said it is seeking further ethical, scientific, and patient advice on the matter.
Richard Horton, editor in chief of the Lancet, said he generally supports making data available to other scientists and patients. But, he said, “When you see some things written on social media [about the ME/CFS trial and the investigators], it makes you anxious that the claims for rational scientific debate based on access to the data may not be fully delivered.” Dr. Horton says the Lancet stands by the trial findings.
James Coyne, a professor of psychology at the University of Pennsylvania School of Medicine, in December asked another journal, PLOS One, which published a follow-up paper based on the Pace trial, to get the researchers to turn over their data. Among his concerns, Dr. Coyne said the researchers changed their outcome measures after the trial began and he wants to see if patients would have shown improvement under the original criteria. A spokesman for PLOS said the journal has contacted the study authors.
Tom Kindlon, 42 years old, of Dublin, and assistant chairman of the Irish ME/CFS Association, says he agrees patient confidentiality must be protected but that the research data he and others want access to “is not the sort of information that would identify people.” A concern he has is that patients in the trial might have reported feeling better, but that objective measurements of their performance, especially how far they could walk in six minutes, may not have shown actual improvement.
Anna Sheridan Wood, 40, a patient from Glasgow, also filed a request for data on the six-minute walking tests, but says the university turned her down. She has filed an appeal. She feels some scientists believe patients cannot be objective when assessing data because of their personal stake in the matter. But she will look at the data with “an open mind, as a scientist,” says Dr. Sheridan, who has a Ph.D. in physics.
Patients who request data aren’t subject to the same rules or controls that professional scientists are, says Stephan Lewandowsky, a cognitive scientist at the University of Bristol, in England, who co-authored a commentary in the journal Nature earlier this year arguing that open access to research data can be abused. Under certain conditions, “you have to say no,” he says. Dr. Lewandowsky has proposed creating an independent body that can weigh in on data requests either from scientists or members of the public “when things are contested.”

Dr. Jonas Blomberg Meets with Carol Head, Zaher Nahle
On Feb. 25, 2016 Solve ME/CFS Initiative President Carol Head and Dr. Zaher Nahle, Vice President for Research and Scientific Programs, met with Dr. Jonas Blomberg, a leading Swedish virologist, at the Solve ME/CFS Initiative offices in Los Angeles. Patient advocate Etel Barbork also visited the offices. During the meeting, a wide range of topics related to ME/CFS research and policy were discussed, including the status of ME/CFS research in Sweden and the rest of Europe.
The group also discussed potential collaborations between the Solve ME/CFS Initiative and Dr. Blomberg’s research group. Dr. Blomberg is leading an effort with a team of Swedish investigators, including: Dr. Carl-Gerhard Gottries, Dr. Per Julin, Dr. Anders Rosén and Dr. Jonas Bergquist, who are collaborating to investigate aspects of ME/CFS using new methodologies.

 
Open Medicine Foundation welcomes Dr. David S. Bell, newest Scientific Advisory Board member  We are pleased to announce David S. Bell, MD, a widely respected medical doctor with extensive ME/CFS experience, has joined our ME/CFS Scientific Advisory Board. 
 "I am thrilled to become part of Open Medicine Foundation for several reasons," said Dr. Bell. "First and foremost is that in the many years I have been studying the illness there has not been the comittment to it by the state of the art science, and that has been mainly because of scientific apathy and/or lack of funds. But the Open Medicine Foundation is starting with the understanding that ME/CFS is not going to reveal its mysteries without real science. It is my hope that I can add to the overall effort with my clinical perspective."
 We invite you to see what distinctive benefits Dr. Bell will bring as we move closer to Ending ME/CFS and listen to his latest public discourse on the disease. See more about Dr. Bell.
 WELCOME DR. BELL!
Linda Tannenbaum, Executive Director
Open Medicine Foundation
www.openmedicinefoundation.org
 
​

Excessive Folate, B12 in Pregnancy Dramatically Ups Autism Risk
Pam Harrison
| May 12, 2016
 
BALTIMORE ― Excessive levels of plasma folate and vitamin B12 during pregnancy have been linked to a dramatic increase in autism risk in offspring, new research shows.
Investigators at Johns Hopkins University, Baltimore, found that when maternal plasma folate levels and vitamin B12 levels are >59 nmol/L and >600 pmol/L, respectively, autism risk is increased more than 17-fold.
The findings were presented at the International Meeting for Autism Research (IMFAR) 2016.
"When we looked at the vitamin supplementation evidence, we saw what our colleagues see ― that indeed, women who took vitamin supplementation during pregnancy had a lower risk of autism in their children and that is very consistent with the literature," principal investigator Daniele Fallin, PhD, director, Wendy Klag Center for Autism and Developmental Disabilities, John Hopkins Bloomberg School of Public Health, said during a press briefing.
"But when we looked at women who had excessively high levels of folate, we saw that very high levels of folate in the mother were responsible for about a twofold increased risk for autism in their child [P = .007], and when we looked at B12, women who had excessively high levels of B12 had a threefold increased risk for their child to have autism [P = .001], while women who had extreme levels of both folate and vitamin B12 had a 17.6 times greater risk of having their child diagnosed with an ASD [autism spectrum disorder] later on [P < .001]," she added.
"So for now, the public health message is, supplementation is good, but there may be a subset of women whose levels are extremely high, and these extreme levels may be harmful."
Led by Ramkripa Raghavan, MPH, investigators analyzed data from 1391 mother-child pairs enrolled in the Boston Birth Cohort, an ongoing, longitudinal study that includes a predominantly low- income, minority population.
The study included children born between 1998 and 2013 who were followed from birth through childhood. At the time of delivery, maternal serum folate and vitamin B12 levels were analyzed. Mothers were asked whether they took a multivitamin supplement during pregnancy and, if so, how often.
A total of 107 infants were diagnosed with autism, Asperger syndrome, and/or pervasive developmental disorder not otherwise specified and were categorized as having ASD.
Investigators noted that levels of both nutrients varied from deficiency levels of plasma folate (<13.5 nmol/L) and vitamin B12 (<200 pmol/L) to excessive levels of plasma folate (>59 nmol/L) and vitamin B12 (>600 pmol/L).
Dr Fallin said that the team was not able to determine whether excessive plasma folate and vitamin B12 levels corresponded to a certain level of intake of both supplements during pregnancy.
"In our study, we were not able to connect precise vitamin use and later folate and B12 levels in these mothers. But, generally speaking, it's important to appreciate that levels of folate in blood are not just a function of supplement intake. They are also a function of diet and a genetic makeup that can change dramatically how easily a person retains or clears folate," she said.
She acknowledged that it is important to establish what constitutes a safe and effective intake of supplements for women during pregnancy.
A Balanced Approach
Geraldine Dawson, MD, president of the International Society for Autism Research and professor of psychiatry and behavioral science at Duke University School of Medicine, Durham, North Carolina, told Medscape Medical News that it has long been known that diet and vitamin supplementation are very important for fetal brain development.
"Now we're also seeing that it's also important for lowering the risk that your child will have autism," she added.
Future research will help to identify exactly what levels of vitamins pregnant women need to take, she said.
"But I think the new finding here is that we've been focusing on the need for supplementation of vitamin B and also folate, but now we're also seeing that we don't want to take too much ― that if you have very high levels of these nutrients, that this is not optimal," Dr Dawson said.
"So the next step is to define what the right level is, but I think the message so far is to take moderate levels of supplements and not to overdo it, but certainly don't 'under-do' it, either."
Dr Fallin has disclosed no relevant financial relationships.
International Meeting for Autism Research (IMFAR) 2016: Abstract 149.004, to be presented May 13, 2016.
 
 
​

It started with a failed attempt. Somehow Suzanne Vernon had prevailed upon Armin Alaedini, a PhD from Columbia University look for antibodies that might be attacking the central nervous system in chronic fatigue syndrome (ME/CFS). He found none but then decided to look a little further - and found evidence of an increased antibody response to gluten in a subset of ME/CFS patients. His finding that the degree of the antibody response correlated with symptom severity suggested that this response could be an important player for some people with ME/CFS.

From Phoenix Rising - March 2016:

 ME/CFS: It Had to Be Different

The really intriguing finding from the study, though, was that further testing suggested that the ME/CFS patients response to gluten was different than seen in celiac disease. Celiac disease is clearly characterized by antibodies to an enzyme called transglutaminase 2 enzyme. One study reported that these antibodies are so prevalent in celiac disease that they exhibit "extraordinar(ily) high .... specificity and sensitivity" for a disease.

They're not present in ME/CFS, though. Something else is happening. In fact, Alaedini believes the response to gluten he's seen in ME/CFS may be unique to the disorder. (ME/CFS just HAD to be different (lol)). That perhaps doesn't surprise patients who have found their disease fall through the cracks again and again but it does set the stage for a possibly exciting (and newsworthy) finding. Given the interest in celiac disease and gluten intolerance a novel finding in ME/CFS would be sure to spark considerable interest.

We hypothesize that the molecular targets of the antibody response to gluten in ME/CFS are unique, further characterization of which may identify novel biomarkers of the condition.
Click to expand...
Of course it would also mean that current celiac testing protocols are not terribly accurate with regard to people with ME/CFS.

Leaky Gut Syndrome and Inflammation

Alaedini's findings - which are publication now - set the stage for a grant application to explore not just gluten antibodies but leaky gut syndrome, the translocation of substances to the blood and systemic inflammation in a subset of patients.

The grant approval was another bit of good news but Suzanne Vernon used her contacts to take Alaedini's research a step further. Shukla's recent study - which Vernon funded while at The Solve ME/CFS Initiative - suggested that exercise may cause the gut to leak substances into the blood causing inflammation and possibly fatigue and pain. Suzanne Vernon prevailed upon Shukla to contribute his samples to the Alaedini study.

Those samples gives Alaedini access to another set of well-characterized patients and a quick validation of his findings. Plus he'll be able to see the effects exercise have on them and vice versa. My guess is that the ME/CFS subset with Alaedini's antibodies will exhibit greater gut leakage and more evidence of inflammation after exercise than other ME/CFS patients.

The Bateman-Horne Center is partnering with Dr. Alaedini to provide samples from ME/CFS patients and controls.

Gut Studies Underway

The gut is getting a lot of attention. We just saw the publication of two Australian studies and Shukla's was published in December. The NIH Project Reporter page reports three studies have been funded in recent years.

• INTESTINAL IMMUNE RESPONSE IN MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME (Alaedini)
• MICROBIAL DISCOVERY AND IMMUNITY IN ME/CFS (Lipkin)
• MICROBIOMES AND INFLAMMATION IN CHRONIC FATIGUE SYNDROME (Hanson - ended 2015)

Drs. Lipkin and Hornig are involved in at least two, perhaps three gut studies. One was funded by the Microbiome project, another I believe was funded by the CFI, and there's' the recent NIH funded study (which provides for sample collection only.)

Invest in ME is funding a leaky gut/microbiome project. Others are surely underway.

The National Institutes of Health is strengthening its efforts to advance research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a disease for which an accurate diagnosis and effective treatment have remained elusive. The actions being taken include launching a research protocol at the NIH Clinical Center to intensely study individuals with ME/CFS and re-invigorating the efforts of the long-standing Trans-NIH ME/CFS Research Working Group with the National Institute of Neurological Disorders and Stroke (NINDS) as the lead of a multi-institute research effort.
“Of the many mysterious human illnesses that science has yet to unravel, ME/CFS has proven to be one of the most challenging,” said NIH Director Francis S. Collins, M.D., Ph.D. “I am hopeful that renewed research focus will lead us toward identifying the cause of this perplexing and debilitating disease so that new prevention and treatment strategies can be developed.”
NIH’s direction on the disease is being guided by a recent Institute of Medicine report , that recommended new diagnostic criteria and a new name for the disease (Systemic Exertion Intolerance Disease), and an NIH-sponsored Pathways to Prevention meeting that generated a position paper and report with recommendations for research strategies.
The symptoms result in significant functional impairment accompanied by profound fatigue. Because the pathology of ME/CFS remains unknown and there is no test to diagnose the disease, studies to date have used different criteria for diagnosis, which has limited the ability to compare results across studies. Additionally, many of the published studies are based on small study populations and have not been replicated.
In an effort to remedy this situation, NIH will design a clinical study in the NIH Clinical Center with plans to enroll individuals who developed fatigue following a rapid onset of symptoms suggestive of an acute infection. The study will involve researchers from NINDS, the National Institute of Allergy and Infectious Diseases, National Institute of Nursing Research and National Heart, Lung, and Blood Institute. The primary objective of the study is to explore the clinical and biological characteristics of ME/CFS following a probable infection to improve understanding of the disease’s cause and progression.
NIH will also be considering additional ways to support ME/CFS research in the extramural research community. Since the root cause of ME/CFS is unknown and the manifestations of the disorder cut across the science interests of multiple NIH institutes and centers, a trans-NIH working group will be needed to assist that plan. NINDS Director Walter J. Koroshetz, M.D., will chair the Working Group along with Vicky Holets Whittemore, Ph.D., the NIH representative to the U.S. Department of Health and Human Services’ Chronic Fatigue Syndrome Advisory Committee. One goal of the group will be to explore how new technologies might shed light on what causes ME/CFS. The Working Group includes representation from 23 NIH institutes, centers and offices.

Researchers have found that two treatments for Chronic Fatigue Syndrome have long term benefits for people affected by the condition.
The team from Oxford University, King’s College London and Queen Mary University of London were following up patients who took part in a study published in 2011, funded by the Medical Research Council. In that study they looked at four potential treatments for Chronic Fatigue Syndrome (CFS) and found that cognitive behavioural therapy
(CBT) and graded exercise therapy (GET) achieved better outcomes than standard medical care (SMC) and adaptive pacing therapy (APT) at one year.
In this study they contacted the people who took part in the original study to find out how they were fairing two and a half years after starting the treatments.
Three quarters of the original trial participants took part in the follow up. It showed that the improvements in fatigue and physical functioning seen at one year in the trial with CBT and GET were maintained in the long-term.
Professor Michael Sharpe from the University of Oxford said: 'The finding that participants who had cognitive behavioural therapy and graded exercise therapy had maintained their improvement over 2 years after entering the trial, tells us that these treatment can improve the long-term health of people with CFS.'
The team also found that participants who originally had CBT or GET were less likely to have sought additional therapy after the trial than those who originally had standard medical care alone or APT.
Dr Kimberley Goldsmith from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London said: 'We found that participants who had originally been given SMC or APT appeared to be doing as well as those who had CBT or GET in the longer term. However as many had received CBT or GET after the trial, it does not tell us that these treatments have as good a long term outcome as CBT and GET.'
There were no significant differences between the four original treatment groups in the number reporting a long-term deterioration in their general health (around 1 in 10 of each group). This showed that there was no evidence that those who received CBT and GET were more likely to worsen in the long term.
Professor Peter White from Queen Mary University of London said: 'Finding no significant differences in the proportions getting worse over time is a reassurance for those who worry that some of these treatments might make things worse. But it is also a reminder that these treatments do not help everybody, and more research is needed into finding other treatments that help.'
See abstract of study at: http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366%2815...

FORT LAUDERDALE-DAVIE, Fla. – Nova Southeastern University (NSU) Executive Vice President and Provost Ralph V. Rogers Jr., Ph.D., recently presented Nancy Klimas, M.D., with the 5th Annual Provost’s Research and Scholarship Award.
The purpose of the award is to recognize a faculty member who has demonstrated significant achievement in support of NSU’s mission to foster scholarship, intellectual inquiry, and academic excellence.
Research and scholarship are two of NSU’s eight core values, and excellence in these areas enhances education, patient care, and public service, and develops superior scholarship.
“We are proud of Dr. Klimas for exemplifying NSU’s Core Values through her groundbreaking research in the field of neuro-immune medicine,”
said Dr. Rogers.
The announcement was made at the External Funding Recognition Reception, hosted by Gary S. Margules, Sc.D., vice president of NSU’s Office of Research and Technology Transfer, at which faculty members from all disciplines across the university are recognized for their commitment to advancing their fields of study.
 “I am humbled by this honor and accept this award on behalf of my team of world-class researchers in the hopes that our discoveries will make a true difference in the lives of those facing neuro-immune disorders,” said Dr. Klimas. “I am proud to be a part of the NSU family and work with researchers in a diverse array of fields.”
Dr. Klimas has achieved international recognition for her research and clinical efforts in multi-symptom disorders, chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME), Gulf War illness (GWI), and fibromyalgia. Among many other honors, Dr. Klimas was the recipient of the 2014 Perpich Award by the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME) for distinguished community service. She also was featured as a “Woman to Watch” on WFOR CBS 4.
She currently serves as director of NSU’s Institute for Neuro-Immune Medicine, professor of medicine, and chair of the Department of Clinical Immunology at NSU’s College of Osteopathic Medicine. She is also professor emerita at the University of Miami School of Medicine, director of clinical immunology research at the Miami Veterans Affairs Medical Center (VAMC) and leads the GWI and ME/CFS clinical and research program at the Miami VA.
Dr. Klimas is a diplomate of the American Board of Internal Medicine and a diplomate in diagnostic laboratory immunology. She is a past president of the IACFS/ME and is also a member of the VA Research Advisory Committee for GWI, the National Institutes of Health’s (NIH) P2P CFS committee, and served on the Institute of Medicine’s ME/CFS review panel.
Klimas has advised three U.S. secretaries of health and human services during her repeated service on the U.S. Department of Health and Human Services CFS Advisory Committee. She is currently funded by the VA, Department of Defense and NIH to study these complex disorders using a systems biology approach with a strong focus on illness models that lead to therapeutic targets and clinical trials.