Jarred Younger on Why Rituximab Works When it Does

[Cort]

Jarred Younger of the Neuroinflammation, Pain and Fatigue Lab posted his thoughts on why Rituximab works when it does. He's proposing a very different reason.

Here is my hypothesis (which is different from other researchers) regarding how rituximab improves fatigue. B-cells are immune system cells that are ordinarily found only in the body (and not in the brain). However, when microglia in the brain are activated, they can weaken the blood-brain-barrier and let in the B-cells. Once inside the brain, B-cells cause inflammation that lead to pain and fatigue. Rituximab depletes the B-cells in the body. Because the B-cells are depleted in the body, there are no cells left to reach the brain and cause inflammation.

Interesting that so far Rituximab gets about the same response rates as LDN. He's not the only one to think that the blood-brain barrier might be involved.

The response rate was very good, with 64% of participants showing a significant clinical improvement of symptoms. That number is very interesting because it is the same response rate I see when I use low-dose naltrexone (LDN) with fibromyalgia. I am guessing that LDN and rituximab provide two different paths to reaching the same goal: stopping neuroinflammation. LDN gets into the brain and calms down the microglia so that the blood-brain-barrier gates remain strong enough to keep out the B-cells. Rituximab depletes the B-cells so they cannot reach the brain, even if the gates are damaged.

There are some negative aspects to mention. The study is small, which means we need to see larger replications. It was open-label, meaning that the results are not controlled for placebo effects. There were some adverse events such as upper airway infections, an allergic reaction, and a temporary worsening of symptoms in some participants. Still, the results are encouraging and reinforce what this group has been reporting for the past few years. The technical aspects of the study look good to me, so I will be very interested in seeing what comes up next for this drug.

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[JennyJenny]

Very interesting. I use LDN and it does help give me a little more peace with my sleep (I am knocked out or at least to get knocked with Zolpidem and also take Gabapentin and Tizanadine) and I do understand his thoughts on this being a Neuroimmune illness but I can't seem to believe in the BBB and it being broken down. (As if I have ANY medical training so why can't I believe in that.) And LDN does cut cognitive, pain and flu symptoms.

At any rate, is there a simple to read BBB article and video that explains it?

And Cort, do you believe it actually exists (BBB) because I am thinking it is more of a theory at this point. I think. I just know I have come across information on it before but couldn't even figure out what they were really saying and if it really existed or was a theory.

 

[JennyJenny]

.

At any rate, is there a simple to read BBB article and video that explains it?

I just know I have come across information on it before but couldn't even figure out what they were really saying and if it really existed or was a theory.

Well look at what I found that I could understand. Now, I understand BBB AND why his B Cells theory makes sense.

http://faculty.washington.edu/chudler/bbb.html

 

[soulfeast]

Jarred Younger of the Neuroinflammation, Pain and Fatigue Lab posted his thoughts on why Rituximab works when it does. He's proposing a very different reason.



Interesting that so far Rituximab gets about the same response rates as LDN. He's not the only one to think that the blood-brain barrier might be involved.





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Mast Cells also disrupt the BBB. There is cross talk between mast cells and microglia.

Brain mast cell degranulation regulates blood-brain barrier.
http://www.ncbi.nlm.nih.gov/pubmed/8951099

Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress.
http://www.ncbi.nlm.nih.gov/pubmed/12438528

Mast cells on the mind: new insights and opportunities
http://www.sciencedirect.com/science/article/pii/S0166223613001124
Highlights
•
Mast cells (MCs) are brain-resident immune cells that serve both as sensors and effectors in communication among nervous, vascular and immune systems.
•
MCs lie on the brain side of the blood–brain barrier (BBB) and communicate with neurons, glia, blood vessels, and other hematopoietic cells via their neuroactive prestored and newly synthesized chemicals.
•
Although small in number, MCs exert powerful effects because they are first responders that act as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation.
•
MCs both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotionality.
•
New experimental tools enabling isolation of brain MCs, manipulation of MCs or of their products, and measurement of MC products in very small brain volumes present unprecedented opportunities for examining these enigmatic cells, both during development and adulthood.

Mast cells, glia and neuroinflammation: partners in crime?
http://onlinelibrary.wiley.com/doi/10.1111/imm.12170/pdf
Mast cells, glia and neuroinflammation: partners in crime?

My daughter and I see Dr. Afrin at U of Minnesota (and diagnosed with MCAS) and he suggested we test for anti-ige/igg antibodies which might then indicate auto-immune driven mast cell activation. The suggested treatment is Rituximab.

 

[SuziRider]

Isn't Rituximab what is used to treat small intestine bacterial overgrowth (SIBO)? Main symptom is a lot of burping hydrogen gas after a meal with carbs or prebiotics. Cause is low stomach acid and the gut bacteria overgrowing. People are not supposed to have much bacteria in the small intestine, compared to the large one. H.Pylori is usually involved, but treating for it alone does not fix the bloating and pain.
SIBO can be detected by a simple breath test (blood tests dont show it) but to me, burping excess hydrogen gas is obvious (methane gas tends to come out the other end and smells nasty!)

With the tie between gut health, pain, and brain health, there has to be something there, whether it is the B-cells or whatever.
If you burp a lot and have headaches or pain, it doesn't hurt to try Rituximab 550 for 2 weeks, PLUS betain hydrochloride before meals and probiotics afterwards for a month or two, to see if it helps.
Bone broth-based soup and a low-gluten diet is also said to help the guts heal, so give them every advantage. Get about 5 gms of Omega3's a day via capsules or fish so as to reduce inflammation, and be sure you are getting extra magnesium, so the guts are in a healing parasympathetic state at night.

Side effects: You might get rid of other health or skin problems, too.

For those here who have tried the above for pain or gut issues, please report back!
Did you do all of the above protocol, or just part? What were your findings?

 

[Remy]

Isn't Rituximab what is used to treat small intestine bacterial overgrowth (SIBO)? Main symptom is a lot of burping hydrogen gas after a meal with carbs or prebiotics. Cause is low stomach acid and the gut bacteria overgrowing. People are not supposed to have much bacteria in the small intestine, compared to the large one. H.Pylori is usually involved, but treating for it alone does not fix the bloating and pain.
SIBO can be detected by a simple breath test (blood tests dont show it) but to me, burping excess hydrogen gas is obvious (methane gas tends to come out the other end and smells nasty!)

With the tie between gut health, pain, and brain health, there has to be something there, whether it is the B-cells or whatever.
If you burp a lot and have headaches or pain, it doesn't hurt to try Rituximab 550 for 2 weeks, PLUS betain hydrochloride before meals and probiotics afterwards for a month or two, to see if it helps.
Bone broth-based soup and a low-gluten diet is also said to help the guts heal, so give them every advantage. Get about 5 gms of Omega3's a day via capsules or fish so as to reduce inflammation, and be sure you are getting extra magnesium, so the guts are in a healing parasympathetic state at night.

Side effects: You might get rid of other health or skin problems, too.

For those here who have tried the above for pain or gut issues, please report back!
Did you do all of the above protocol, or just part? What were your findings?

No, that is rifaximin brand name Xifaxin. It's an antibiotic that stays local to the gut and is totally different than rituximab.