News From Jarred Younger / Neuroinflammation, Pain, and Fatigue Laboratory at UAB, From Aug 2020

My (slightly hurried) notes on what Professor Younger says:

1. The brains of people with ME/CFS are hotter (99.5 to 102 degrees F) than those of healthy people (healthy 97.5 to 99.5 degrees F)
The work done with the Solve ME grant (15 people with ME/CFS) was promising enough for the NIH to fund the study that is underway (>100 people). They are a good way through that study, Younger seems to expect it to confirm that most people with Me/CFS have an elevated brain temperature, he thinks it will be very helpful for the field.

2. The increased temperatures causes the symptoms i.e. sickness behaviour.
[Does it though? Maybe the mechanism is not entirely due to the temperature, might be due to the cause of the increased temperature.]

3. He thinks the raised temperature is due to inflammation (i.e. microglia are in activated state - demanding more oxygen and glucose, generating heat that is trapped within the brain)

3. Other possible causes of raised core body temperature
Raised core body temperature (fever)- no
Cerebral perfusion problems.

They do occasionally see hypoperfusion when the participants are scanned (note, they are lying down) - Younger thinks this is a problem (seen in around 10% of the people they scan) but he doesn't think it is ME/CFS.​

Tumours, traumatic brain injury
Autonomic dysfunction

4. Can cooling the brain down relieve symptoms?
Younger doesn't know, but he's interested to see. there are big expensive devices that cool the brain.

5. Are leucocytes (t-cells, b-cells) entering the brain (where they should not be) and activating the microglia?
Can the leucocytes be found in the brain in ME/CFS?
Can do a PET scan using a ligand to track leucocytes. Until now, the problem is that the ligands only last for a day, and you need a ligand that remains visible for several days, because that is how long it takes for the leucocytes to get into the brain. Younger and colleagues identified Zirconium89 ligand - the leucocytes can be taken out of the person, tagged and returned, and the tracer is visible for days. It's taken a lot of work (6 years) to identify the solution, get approvals etc. They have done 4 healthy controls and it's working really well. The leucocytes stay in the blood supply e.g. in the lungs, even after 72 hours, but do not get into the brain.



They haven't done the procedure on an ME/CFS participant yet. Younger is excited - he will release the information when the images are done, maybe 2 to 3 months from now.

6. Are the microglia activated?
There is an inflammation marker (a radio-ligand, DPA714) that labels only activated microglia.They are working on this; they will also be doing this in Long Covid. Younger seemed to be suggesting that there are particular parts of the brain that have the activated microglia, but he didn't actually say that.

He looked on Clinical Trials. gov, noted that there are 20 current treatment trials there for ME/CFS. There are lots of behavioural ones. [A bit heart-breaking to see the waste of money and effort]
Long Covid has 200-300 current trials. He is keen to push ahead on treatment trials. He thinks what helps for one of ME/CFS and Long Covid, is likely to help for the other.

He identifies a large list of drugs and botanicals that he thinks are worth testing. He seems very keen on low dose naltrexone - he seems to believe it clearly helps some people and doesn't help others. He believes that they need to find out why not everyone is helped and look at some new versions of naltrexone. They are doing a large clinical trial on cucurmin, resveratrol, stinging nettle. He mentions vagal nerve stimulation as calming activated microglia.

He would like to see a dedicated clinical trial centre for ME/CFS. He acknowledges the good work organisations like SolveME do in funding preliminary research.

Younger's team is running decentralised clinical trials, so people elsewhere in the USA can participate, so people should watch out for that. He encourages participation in studies. He says, if you are interested in the science and have skills, talk to the Principal Investigators. If you have skills in neuroimaging, in clinical trial management etc, talk to the scientists, as they are having trouble finding enough skilled people.

My overall impression was that he has a big and busy team, and he feels quite confident that he is on the right track. I think his core work is interesting and I look forward to the results of the studies that are underway. I have reservations about his enthusiasm for some of the possible treatments e.g. I don't think we've yet seen good evidence for low dose naltrexone or vagal nerve stimulation working in any diseases really.

 

for those of us who haven’t managed to watch the video what do the columns represent?

 

Threads now set up here:
University of Alabama - Men with FM and/or ME/CFS for study of chronic pain and fatigue
USA - University of Alabama - Brain imaging study on women with ME/CFS