1:20 - How things have changed with our federal agencies (US):
[7:14:06 on in-video clock]
Thinks it's time to forgive and forget, as they are now starting to ramp up support dramatically.
(Centre for Disease Control) - now running a multi-site clinical assessment (MCAM).
- Involving 7 CFS specialist clinics around the country, including theirs. 470 patients in 2013. Questionnaires, physical exam, NASA lean test, neurological, exercise, cognitive testing, biological samples. Adding paediatric, early onset, home-bound groups plus chronic illness controls (from other diseases). Will be studying NK cell function.
First publication coming soon describing the methods. Good longitudinal data and will enable many studies using this.
+ 4:00 - CFSAC (Committee to the secretary of health) https://www.hhs.gov/ash/advisory-committees/cfsac/index.html
Been meeting for years, but it's been ignored. Now functioning more as intended. 13 members, including biomed science, pub/private health care delivery, carers, etc.
[Trying to fix issues with slides.]
6:39 [continues] - an active group making recommendations to the secretary and NIH. Representatives from each major agency of federal government. So check them out.
+ 7:18 - IOM (Institute of medicine)
report [10 Feb 2015], was very pivotal. Federally funded but outsourced for neutrality. Year long review to come up with new clinical criteria for diagnosis. A subtle change, but evidence based report is respected by all of medicine and academia, taken note of, opening doors.
(Including PDF downloads.)
+ 8:30 - P2P (Pathways to Prevention)
report - another evidence based review within NIH, done in in parallel.
+ 8:58 - Director of NIH
released a statement a year ago, stating they were going to take ME/CFS seriously. A huge change.
Explaining what the NIH is, it's structure. They do basic research in house plus fund other researches inside and outside the US in some cases.
Now there is an inter-agency collaborative (within health and human services):
+ Trans-NIH working group
Headed by Dr Koroshetz, director of NINDS, and Vicky Whittemore (amazing person and catalyst), also a member - NIH representative in CFSAC.
They can review grant applications, and send worthy projects to the best place for funding. Their overall goals - to advance, encourage and communicate ME/CFS research.
+ 12:34 - NIH intramural study
Planning a protocol, bringing patients in for extensive testing [Autumn 2016]. The best you could hope for. Looking specifically for patients with viral onset, well evaluated and sick less than 5 years. Looking at the illness from an earlier window.
Announced (notice of intent) funding of 2 opportunities:
1) For collaborative ME/CFS research centres.
2) Data management and co-ordinating centre.
Doing things the way they should have been from the beginning. We're hoping this will come before the end of January, with directors of agencies being changed after an election.
15:03 - What do we already know about ME/CFS?:
- Function impaired systemically. Characterised by PEM.
- CNS and autonomic involvement (from sleep, cognitive, pain, orthostatic intolerance). Many supporting studies came out after the IOM report and for P2P, including imaging, cerebrospinal fluid, tilt testing and lean test.
- Immune disturbances, including NK cells and cytokines. Phases of diseases presenting differently.
- No new name can be decided.
- Case definitions don't work well.
- Similar symptom overlap with FM and POTS.
- Not been able to produce good biomarkers.
- pwME/CFS have been suffering without good support for decades.
* 18:00 - What did she learn in October in Sweden and at IACFS?:
listing speakers, posters, etc, summarising content.]
on the Swedish conference. Full day video
(partly in English).]
Scientific research clearly and definitely supports it is a biological disease. We're not going back and research will now advance exponentially. Clinical medicine is totally unprepared for what's going to happen.
18:50 - From specific presentations (diagnostics available now):
- From Romberg and lean tests you can pick out persons with abnormalities, with correlation between the results from each.
- 10 minute NASA lean test comparable to tilt-table (which is hard to get, so good alternative).
- Cognitive testing tailored for ME CFS are coming soon, narrowing it down. They've previously been long and difficult to get.
- Tests for small fibre Polyneuropathy.
* 21:05 More possible treatments and tools:
- Dr Jarred Younger
- Low dose Naltrexone (LDN) works better than opioid in FM patients.
- Dr Peter Rowe
- treatments for orthostatic intolerance and POTS. Just need doctors to recognise this problems separately.
- Dr Jon Kaiser
- pushing through FDA approval for one of the first treatments: methylphenidate [Ritalin] micronutrient supplement. Once first drugs are validated it would also validate the illness.
- (23:00) Rituximab (used for non-hodgkins lymphoma and rheumatoid arthritis) - makes CFS/ME responders able to return to work. Very slow effect. Culls B-cells, reduction in whatever auto-immune process, B-Cells grow back and illness recurs.
- Dikoma Shungu
- proton magnetic resonance spectroscopy (MRS) research. A way of imaging chemicals in the brain. Previously shown increased lactate and reduced glutathione.
Administered N-Acetylcysteiene (NAC, as given in emergency for tylenol overdose), showed with imaging that glutathione was restored and that symptoms improved.
Note taking them orally won't necessarily get the NAC to the cells where it's needed.
* 25:12 - New objective biomarkers upcoming:
- Dr Jose Montoya
's group (at Stanford) - cytokines in blood are different from controls after an exercise challenge. Also, more cytokines = sicker. Genomics showed pattern consistent with systemic inflammatory response.
- (26:33) Microbiome - intense interest in all fields. Reduced bacterial diversity, changes in the virome too. Starting to look at it as a diagnostic, also understand the physiology.
- (27:30) Metabolomics - 2 unpublished papers showed a specific signature in the blood.
- Mitochondria, and how they relate to the illness.
- Cardiopulmonary test, the lactate in the blood rises more and more quickly, possible marker. There is a low anaerobic threshold.
* 28:38 - Some general themes:
ME/CFS is a hypometabolic state, on a cellular level, from metabolites.
(29:37) Maureen Hanson - study (unpublished), it look most like over-training syndrome (in athletes).
The metabolic products from several pathways are gender and control distinct.
Sphingolipids stood out as most significant. (Biochemistry is beyond her comfort zone) but these are important part of cell membranes and particularly associated with nerve and brain cells.
* 33:27 People at Swedish [?] conference:
(virologist) and Anders Rosén
(B-Cell specialist), in Sweden (both very distinguished). Reviewed the [Naviaux?] metabolomics paper.
(B-Cell specialist in London) - part of lab that first showed Rituximab would work for auto-immune disease too.
(also at IACFS/ME) - oncologist from Norway who's studied Rituximab in CFS.
Dr Per Julin
- Swedish neurologist has rehab clinic for other diseases, now including CFS patients, taking high tech imaging.
(35:25) Blomberg - gave preview of paper. Gut microbes help train immune system, learning what's self and foreign. If gut permeability changes, then new pathogens my trigger immune system response.
Certain B-Cells are involved in auto-immunity. In primary biliary cirrhosis there are anti-mitochondrial anti-bodies and patients have PEM.
(37:30) Rosén - on metabolomics paper and sphingolipids: viruses exploit and manipulate membranes, e.g. HIV, rhinovirus, measles, ebola, hepatitis C, influenza. Also Epstein Barr viruses modify lipid raft micro-domains.
(38:50) Japanese group showed TCA cycle is abnormal [picture]. Fluge and Mella also think there's disruption of ATP in cells. Don't know which cells in body. [Artificially] disrupting this at various points and then comparing the metabolites seen could help pin this down.
(40:58) [Enlargement of Mitochondrial membrane - proteins, etc]
(41:42) Why does B-Cell depletion help? Auto-immunity has not been so much part of the thinking in the US, more so in Europe. But B-Cells are what make anti-bodies.
Rosén's hypothesis [like Naviaux's] that mitochondria are a regulating hub signalling the cell nucleus and circulation. Inflammatory signalling, etc. bacterial trigger activates B-Cells, then they get confused and attack some kind of normal tissue.
(42:55) Some studies presented showed certain allergies more common (in ME/CFS).
Mast Cell Dysregulation [MCAD] - they release histamine. Some may be overactive, could also be a membrane issue. Cause POTS, chemical/drug sensitivities.
* 44: 14 - What's next? Exponential growth. The end.
Bateman Horne web centre links:
+ 44:52 - The auto-immune angle.
Many different viruses can result in post viral syndrome. Lots of studies now, micro-biome, metabolomics, starting to change the perspective now, but need to remember everything from before.
Things are really changing and you should have hope.
Biggest problem is we don't have clinicians who can look after patients. Needs to trickle down into medical schools. Training clinicians is something the Bateman Horne centre is trying to do.
+ 47:45 - Did Montoya's exercise study look at same chemicals as Dr Light's?
Alan Light only looked at a few cytokines and there have been a lot more looked at in many more studies since.
Cytokines vary all the time, depending on context, so hard to make sense. So exercise response test was interesting.
(48:47) Dane Cook (exercise physiologist and PhD) - looked at gene expression in exercise, as with Alan Light, but results varied, due to different types of exercise. Hypothesised that we might tolerate intense exercise better than prolonged, based on this.
Dane's unpublished study (with SolveCFS and biobank) - showed clear changes in cognition after exercise provocation.
+ 50:37 - Rituximab - are they looking at the difference between (non)responders?
They've devised a 3 year study of repeat dosing, so during this time they've been reassessing their data.
Enbrel (another immune modulating drug) they tried but had to stop because patients immediate got significantly worst.
Cyclophosphamide - used as chemotheraputic, seems to work, but has much worst side effects.
They're collected a huge amount of very valuable data.
+ 53:10 - ME/CFS has to compete with all those blockbuster diseases for funding, are we getting somewhere now?
Yes, well we've had an invisible fraction of the total funding. We need to study the underlying processes and it will aid other diseases and funding will grow when there's this overlap.
Once we've had a couple of good papers there will be a lot more people taking interest. The metabolomics paper jump started a bunch more. The samples are already available, so they can be just run through like a lab test.
+ 55:25 - Money for NIH centres might include Bateman Horne?
Possibly. They collaborate with the CDC site[?], who could apply for money. Also Ian Lipkin, because they don't have a clinic so have agreement with a number of clinics. Would love to see money come in.
+ 56:35 - LDN (low does naltrexone) verses Opioids?
LDN is the opposite, it blocks opioid receptor. It calms glial cells in CNS immune system (as per Dr Younger). When the release cytokines sometimes surrounding neurons are harmed. It's as effective for FM pain as approved drugs. But there are all kinds of pain from other sources. And you can't take LDN with opioids as their effects cancel out.
Lyrica, Cymbalta, Savella are the FDA approved drugs for FM. Naltrexone is used in recovering drug addicts to prevent them getting a high from relapse, but dose is far about 1/10th, so needs a compounding pharmacy. But makes it very cheap ~$30 per month.
+ 1:00:00 - Side effects from LDN?
No big studies yet. Can be a bit activating, nightmares, (extra) sleep problems. But generally well tolerated in FM, less so in ME/CFS. Need to do trials across different conditions to find out fully.
+ 1:01:22 - 'Ōura' ring study (Via Dr Suzanne D Vernon.)
The study was a pilot with 20 rings [shown]. Has been picking up the different physiology in ME/CFS people (body temperature, etc), so may not give out the same interpreted information as with healthy people, hence why it was developed.
With traditional polysomnography - terrible as only studies one night of likely bad sleep, all wired up in lab, cost ~$2000. Ring can be worn for months of continuous data, $300-$400. Not sure where we're going to go next. Could buy one online, made in Finland. Uploads data to smartphone, etc. https://ouraring.com/
End. (Everybody's ATP has run out, heh.)
There's going to be this huge progress in research and such, but there we will still have this huge problem in lack of programs and care. Need to make demands of our politicians and help to make progress fast.