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

Jarred Younger: 077 - Seeing what I see: brain inflammation


ETA AI summary:
Summary: Brain Inflammation Patterns in ME/CFS Patients (Video Transcript)

0:00 — Introduction: Exploring Brain Inflammation Data​

The speaker begins by describing a Sunday research session in the laboratory. They have been analyzing MRI and PET scans from participants with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The images visualize neuroinflammation by using a tracer, 11FPA-714, which binds to activated microglia. Brighter red areas indicate higher inflammatory activity. By examining these scans, the researcher aims to understand where inflammation occurs in the brain and whether it follows specific patterns.

1:52 — Baseline: Healthy Control Example​

The first scan shown is from a healthy control subject. As expected, there is minimal neuroinflammatory activity, with only faint background signals caused by resting microglia. This example serves as a baseline for comparison with ME/CFS patients.

2:18 — Pattern 1: Localized Bilateral Inflammation​

In the first ME/CFS case, the inflammation appears as distinct, symmetrical hot spots in the amygdala and hippocampus—areas crucial for emotion and memory. Additional activity is seen in the periaqueductal gray (PAG), a region involved in pain modulation and anxiety responses. The researcher speculates that this pattern might be linked to symptoms such as anxiety and widespread musculoskeletal pain, similar to fibromyalgia.

3:35 — Pattern 2: Widespread Brain Inflammation​

The second group of ME/CFS scans shows diffuse inflammation throughout the gray matter, meaning nearly all neuron cell bodies exhibit inflammatory activity. Although this inflammation is less intense than in localized cases, its widespread presence might lead to many mild-to-moderate symptoms across cognitive, sensory, and emotional domains. The overall impact may still be significant due to the cumulative burden of numerous symptoms.

5:00 — Pattern 3: Brainstem and Thalamic Involvement​

The third group shows intense inflammation centered in the thalamus, midbrain, pons, and brainstem. This pattern closely resembles results from an earlier ME/CFS PET study by Dr. Nakatomi (over 10 years ago). Even though the inflammation is localized, the affected regions are essential for nearly all brain functions, potentially leading to widespread symptoms and post-exertional malaise (PEM).

6:06 — Reflections and Next Steps​

The researcher emphasizes that these are preliminary observations, not formal hypotheses. Further analysis—linking imaging data with symptom reports and performing statistical testing—may alter the current groupings before publication. The video aims to reveal the messy, iterative process of scientific discovery, rather than the polished final version found in papers.

7:00 — Conclusion: Evidence Supporting the Inflammation Hypothesis​

The preliminary findings support the hypothesis that ME/CFS involves brain inflammation. The researcher plans to continue analyzing data, finish a separate brain lactate paper, and provide future updates as more insights emerge from this ongoing investigation.

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He seemed to say "[11F]DPA-714" but based on my limited knowledge (Fluorine-18 and Carbon-11 are radio-isotopes, Fluorine-11 is not?) I'm guessing he meant [18F]DPA-714 or [11C]-PBR28? Or can you mix and match the radio-isotope and the TPSO connecting-part and get [11C]DPA-714?
 
Chandelier said:
Jarred Younger: 077 - Seeing what I see: brain inflammation


ETA AI summary:
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If what Younger presents in this video holds up then this is absolutely huge. But I guess we have to wait for the paper to make any real judgement. He says he's working on a brain lactate one first so might be a while.

I've been quite skeptical about some of his recent statements, but I'm interested to see how this plays out.
 
PolyBio cofounder Dr. Michael Van Elzakker described his lab’s research on neuroinflammation in Long Covid and pre-2018 ME/CFS. Via their PET scanning methodology, biological markers in patient samples (i.e. L-selectin, fibrinogen) are found to be correlated with neuroinflammation identified on imaging.
 
Jarred Younger: 078 - How I am going to fight brain inflammation


Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory, outlines his plan to advance a treatment specifically targeting brain inflammation, which plays a key role in ME/CFS, fibromyalgia, and long COVID. He explains that no existing drug has been designed to directly modulate microglia, the immune cells responsible for neuroinflammation. Current treatments, such as low-dose naltrexone, only reduce inflammation as a secondary effect and come with limitations.

He highlights a promising candidate—dextrorphan (referred to as dextrone/dextronome) dextro-naltrexone—which has shown strong scientific support for microglial modulation for more than a decade, backed by researchers like Linda Watkins and Mark Hutchinson. Although he has long wanted to test this compound in human clinical trials, progress stalled because the idea is already publicly documented, preventing patent protection. Without a patent, companies cannot secure profits, making investment unlikely despite encouraging animal studies.

Because no one has moved it forward, Dr. Younger has decided to take the lead himself. He acknowledges the process will be long, expensive, and high-risk, estimating around 5 million USD to reach early clinical trials. He is seeking donors rather than investors and provides a university-managed donation page where supporters can contribute. He plans to give occasional updates and encourages viewers to watch his earlier video explaining how the compound works.
 
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Sounds like he's pretty convinced neuroinflammation is the cause of ME/CFS and others. $5m may be a pittance in this age of billions and unicorns, but you have to have some conviction to move forward with the project that requires committing years of effort and fund raising to develop the compound.
 
poetinsf said:
Sounds like he's pretty convinced neuroinflammation is the cause of ME/CFS and others. $5m may be a pittance in this age of billions and unicorns, but you have to have some conviction to move forward with the project that requires committing years of effort and fund raising to develop the compound.
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He does seem pretty convinced. But I’ve seen plenty of researchers spend years on something that was very clearly a dead end in hindsight, but they had just enough noisy data to see what they wanted to see. More than I can count, really. Publishing the data proving chronic microglial activation would be a necessary step before asking for public funding for a trial.
 
jnmaciuch said:
Publishing the data proving chronic microglial activation would be a necessary step before asking for public funding for a trial.
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That's my thought. And my guess is that he feels pretty confident about the paper he is about to publish. I'd contribute myself if the paper pans out -- a chance at being able to jog 4x150m without crashing the next day will be worth substantial sum to me. He's asking donation to fabricate the compound, and get it approved, btw. He'll have to have the compound before he can trial.
 
OrganicChilli said:
Has he submitted the paper for peer review yet?
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Not yet, he said he needs to finish his paper on lactate first. But they have published a similar paper on FMS about a year (?) ago and it doesn't appear to have made a definitive impact. The inflammation for ME/CFS that he showed on the video appears a lot more wide-spread and definitive than those for FMS though. I guess we'll have to wait and see.
 
Dextro Naltrexone - From the LDN Research Trust site:


ldnresearchtrust.org

LDN Research Trust

The LDN Research Trust Charity works to raise funds for research trials. We have helped over 100,000 people obtain LDN from a General Practitioner or Consultant, either through the National Health Service or by private prescription. We are proud to have
ldnresearchtrust.org ldnresearchtrust.org


'Naltrexone, taken at the full dose of 200mg daily, has been licensed for use for the treatment of addictions since 1984. (5) It is currently used for both opiate and alcohol addiction, as a full dose is able to completely block endogenous (endorphins released by the brain) and exogenous (recreational drugs such as heroin) opiates. In the licensed dose, it is used as an oral tablet, a long-acting injection, and as an additive in painkillers to prevent them from being abused. (5)

As have many drugs that have been widely used for an extended period, naltrexone has been found to have different actions when used in lower doses than originally intended. These in part are due to the chiral nature of the molecule and the different, dose-dependent effects of the Levo and Dextro isomers of naltrexone.

The concept of chirality is not new, (chiral chemistry was discovered by Louis Pasteur in 1848), like all drugs when synthesized are produced as a racemic mixture of 50:50 left- and right-handed molecules. (6) Half of the mixture synthesized is a left-handed shape and the other half is a right-handed shape. Although consisting of the same components, and being chemically identical, they have different shapes (as with left and right hands), enabling the different isomers to interact with different groups of receptors in the body.

In general, most drugs only have biological activity in the human body in Levo (left) handed shape, as this is how most of the receptor groups in the human body are arranged. Common examples of these drugs—such as levothyroxine, levocetirizine, levobutanol—are manufactured as racemic mixtures of 50:50 Levo and Dextro isomers; however, the manufacturer discards the Dextro isomer and presents the medication in the Levo-only form, sometimes because the Dextro isomer carries unwanted side effects, or is not active on the intended target receptor. (7)

In the case of naltrexone, the Levo isomer interacts with the commonly understood opiate (endorphin) receptors group and the Dextro isomer interacts with the toll-like receptor group. (8) (9)

The basic effects of LDN can be summarized as follows:

DEXTRO-Naltrexone

  • Blocks (antagonises) some TLR receptors
  • Reduces production of pro-inflammatory cytokines
  • Suppresses cascade inflammation
  • Central and system effects as TLR receptors are present on microglial cells, mast cells, and macrophages
LEVO-Naltrexone

  • Blocks opiate receptors for a brief period
  • Increases natural production of anti-inflammatory endorphins
  • Upregulates opiate receptors
  • Has direct effect on some cell proliferation rates
 
Unconvinced. If this is the same data as previous videos where he’s stated only 35% of cases had the inflammation.

He should not be taking money until he has a paper proving this. Again spreading the limited funding of ME/CFS for influencer scientist with the best YouTube channel, not strong hypothesis’s.
 
jnmaciuch said:
I’m really confused by this video. LPS are structures on the outside of bacteria that immune cells recognize during bacterial infections through TLRs. This is just a model of immune response to actual bacterial infection.

And as far as I knew, all the PET tracers for “activated microglia” had serious interpretational problems. None of them were actually for cytokines so it’s just using a certain protein as a proxy for a “activated” phenotype that is itself a big oversimplified category. Has he provided any details for how “activation” was determined?
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ChronicallyOverIt said:
Another video stating activated microglia as fact without data, though this time he lets slip only 35% of people with ME/CFS have (according to him) activated microglia. If this is his new results I’m unimpressed. Also in what world is injecting endotoxin the same as ME/CFS.

How many more videos is he going to make on his imaging that he isn’t making public, while stating this as fact. I’m convinced he’s posting weekly for the YouTube algorithm.
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^ old posts where he discusses this same data where he admits the 35%. Watch that video it’s not confidence inspiring
 
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