Source: Solve ME/CFS Initiative Date: May 28, 2019 Time: 17:00-18:00 UTC URL: https://register.gotowebinar.com/register/4701892549916870924 Whole Genome Sequencing and Analysis of ME/CFS ---------------------------------------------- Please join us on May 28th at 10:00am PT // 1:00pm ET for a Solve M.E. Science & Discovery webinar with Dr. Liz Worthey and Dr. Camille Birch. The discussion will center on their Ramsay-supported whole genome sequencing study. Using a comprehensive genomic and informatics approach, Drs. Worthey and Birch are exploring the hypothesis that ME/CFS in an individual may be caused by a genetic alteration(s) in one or more metabolic pathways, leading to an unstable cellular energetic state, and that the course of illness is based on the type of variant or where in a metabolic pathway an individual's defect lies.
Able to re-watch at Code: https://www.facebook.com/SolveMECFSInitiative/videos/1259381444211871/ Make sure the sound is turned on if you can't hear anything by clicking on the speaker icon.
Thought this was pretty interesting. A number of the slides from it. Note that they have only analysed 10 patients at this stage. Also interesting to hear that one of the researchers had a meeting with in the UK recently with an unnamed researcher here who is keen to collaborate with them.
I've just watched it. I thought it was one of the most fascinating talks I've heard, both on what is being discovered, and on the way they are going about studying the patients, tying their individual genetic data with a detailed questionnaires and patient stories from each patient. Only 10 patients so far, but they are finding out a lot that might turn out to be applicable to others. I guess I was particularly fascinated because it's just the sort of work I would have loved to be involved in if I had studied genetics now instead of 50 years ago.
I can't understand why they say that infections are most often flu. ME was never associated with flu; when Simon Wessely followed people with flu and decided none of them developed ME it was seen as his usual way of seeming to help but deliberately sabotaging the work. ENTEROVIRUSES, ENTEROVIRUSES. Maybe not everyone, maybe not very much, but don't throw away decades of knowledge on the disease you are studying. There are a lot of us.
This is a fascinating talk indeed, and I am very curious and excited about what these researchers will find. The 10 patients were collected from Younger's group "to qualify as unexplained pain and fatigue". I hope they know PEM (or apply CCC/ICC)... They say they are researching ME/CFS/SEID/FM, but "unexplained pain and fatigue" is not ME/CFS; maybe they just don't mention it? This is not supposed to devalue what they're doing, just honest confusion.
Off the top of my head I think Younger might use Fukuda but happy for someone to confirm I'm wrong on that. I do know for certain that Solve are insisting that any application this year has to use criteria that includes PEM.
Yes, Jarred Younger uses Fukuda. I am delighted to hear that Solve are insisting that applications this year must use criteria that includes PEM... I hope that means PEM is mandatory in all patients selected. Otherwise as the doctor working on the Intramural study once said, his name escapes me... Garbage in, garbage out.
Webinar now available on YouTube if people prefer to watch that way. https://www.youtube.com/watch?v=nIJX-Q7w_Z4
Interesting that AMPD3 gene was flagged (frequency of 6% in population, 50% in pwme (10)). She mentions https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1, which has some interesting overlaps. Obviously not a 1 to 1 situation but pretty interesting. I'm not sure if the mutations led to more or less enzyme activity (or if they were the same mutations).
Interesting that iron metabolism has popped up again. It doesn't seem to be something that's been on the radar much before but it's shown up unexpectedly in at least three recent studies. Neil McGregor mentioned it in his Emerge talk and I'm sure it was mentioned as an aside in a third talk (Morten??? ETA: actually I think it was Lipkin) fairly recently, too. I hope they all talk to each other to compare notes. Iron is particularly interesting to me as someone with 'atypical' hereditary haemochromatosis (HHC). In typical HHC when you get treated all your iron measures drop in concert. In my version of HHC, and I'm told this is a known but rare phenomenon, some iron measures drop quickly with treatment but others remain stubbornly high: With treatment, my ferritin, which is an intracellular iron storage protein, is low. At the same time, the two measures looking at iron circulating in the blood, serum iron and tranferrin saturation, are high. Only extremely aggressive treatment brings them down into the normal range but that also leads to my ferritin becoming too low. Can't win. On the face of it that seems to fit Dr Birch's speculation that in ME maybe iron struggles to get into the cells leading to a sort of anemia in tissues but not in the blood. Dr Birch didn't mention this but too much iron floating around the blood can lead to increased ROS damage, something that conceivably could also play a role in ME. Not saying HHC and ME are directly connected, only that if you're unlucky enough to have both the problem of getting iron form the blood into the cells (if there is such a problem) becomes magnified.
Have listened to the whole thing now. She seems to key in on 3 possible sub-groups. Obviously it's a very small pilot study. But the patients with iron genes reminded me of this cort article. Bascially, a young man benefitted to from very high infusion iron, to the point he was way above normal values in the blood. He was about 80% better at that point, and had very limited PEM. Obviously he had enough iron in his blood, so he might fit into this tissue-iron deficient (who knows how you test for that) or some conversion/binding/activation problem subgroup. I don't know what happened to him since the article and to be honest I don't know much about iron problems/testing to talk about it in depth. So, this is a small pilot study with possible subgroups identified and possible actionable steps. Another subgroup involved things that could certainly relate to Naviaux's hypothesis (mtor/ampk findings) and more traditional metabolic diseases. So it's very exciting and the author seems very on point - understanding age groups, onset patterns and reading patient's descriptions of symptoms. Highly recommend listening to the video to anyone interested. Researchers are started to make early headway into subgroups.
Plummer-Vinson syndrome a rare genetic syndrome features Anaemia and sometimes M.E (know someone with both and transverse myelitis) Seperate comment Underactive rather than overactive in this area is it ?https://en.m.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway
Two concerns with Cort's article: One, the teenager described was clearly very unwell; I doubt he was unwell with ME though (Cort routinely confounds PEM and post-exertional fatigue, and I think he does so in this case, too). Two, Cort gives no warning about the dangers of excess iron (though some commentators do so further down). It's true we can't live without iron. It's also true that too much of the stuff can slowly kill you. So please, please, please nobody rush out to try some iron supplements without getting tested first!
Some comments : a) Hemochromatosis / Haemochromatosis (cc : @Ravn) has been discussed and its association with Liver Disease : https://www.mayoclinic.org/diseases-conditions/hemochromatosis/symptoms-causes/syc-20351443 b) Glycogen storage diseases were mentioned. Observe G6PC (=Glucose-6-phosphatase) below : A close call by Network Analysis, generated in 2017, glucose-6-phosphatase node is there (=6GPC, bottom left ): c) Regarding iron, Machine Learning identifes it (entry named "heme_biosynthesis" ) on the first run below : Both of these slides were shown at my presentation at EUROMENE
Thread on the Ramsay award to these researchers, https://www.s4me.info/threads/smci-...uencing-and-analysis-of-me-cfs”-worthey.6112/
Moved post Meanwhile, I just saw this - a genetics study which seems to have something in common with several research papers recently. https://www.healthrising.org/blog/2...FIVF4DldA7XKVvy98Fr0ROaem8rhPlWp0sS40sFIVibGY
