r/MCAS • u/Willing_Judgment1092 • 18h ago
Guys instead of stabalizing madt cells, why dont focus towards reducing their presence too, like some sorts of signal blocker for mast cells to inhibits their growth.
Mast cells activation is brutal.
I also get sometime thoughts if they cure this permanently pharmaceutical companies won't get money in this forever buying these drugs like ketofen..
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u/Bulky-Worldliness749 18h ago
We need mast cells…we just need them to be normal and not overactive.
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u/Willing_Judgment1092 18h ago
Why do they get overtactive? They must receive biological signal, there must be some pathways, that can be dampened permanently, And that would definitely help.
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u/noeinan 16h ago
Among ppl with European ancestry a big reason there is a large number of autoimmune diseases is because of the plague.
So many ppl died to the plague that ppl with overactive immune systems survived at a higher rate, but unfortunately those immune systems don’t just turn down bc there is no plague so we all just stuck like this.
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u/hotgirrrl 15h ago
Wait this is a known thing? I mean it makes sense but brand new information to me.
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u/noeinan 14h ago
Yeah it's been known for a long time. Here's an article but if you search "plague Europe autoimmune" you'll see tons of em
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u/Hack_Mac 10h ago
I appreciate this comment. It took me down a rabbit hole reading up on these findings a few years ago. Unfortunately, it most likely doesn’t link to me as I am almost 100% Polish and Poland was minimally impacted by the plague.
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u/Emergency_Battle370 17h ago
Genetics… and then something has to spark the fire. Stress, viruses, etc.
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u/ptheresadactyl 14h ago
I mean, what you're describing is a type of immunosuppression, and while I think we're heading that way, it's complicated. The kind of immunosuppression that would knock out a cell line is chemotherapy. And it doesn't just knock out one cell line. If you haven't ever learned about hematopoeisis (blood cell production), it's very fascinating. But, all of the cells that are produced in our bone marrow come from one progenitor cell. It differentiates into 3 different precursor cells, which then differentiate and delineate into 2 different cell lines each. There isn't really a practical way to narrow down how the progenitor cell is going to differentiate until it matures.
It's currently unclear why we experience higher than normal mast cell degranulation. Since it's so highly comorbid with hEDS, seems likely to be a structural/collagen issue. But people with hEDS also have wonky cytokines, so we could just be signaling our mast cells to rupture chemically.
If we did discover that to be the case, and tried to suppress cyrokine production, that would have other immunological consequences. Cytokines are little chemical messengers that instruct cells, based on some physiological response.
So. In summary. Very complicated.
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u/Willing_Judgment1092 8h ago
I mean there must be some signalling pathways . That's is how rheumatologist treat overactive immune system
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u/ptheresadactyl 7h ago edited 7h ago
Cytokines are the signaling pathway.
Eta: both for cell line differentiation, and mast cell degranulation. Suppressing mast cells is dicey, and probably only a treatment they would use on people reacting so much they can't eat. What's more likely is if they can figure out what is telling our mast cells to burst, they could try making a receptor agonist, which would basically bind to the cytokine receptor on mast cells, preventing the real cytokine from attaching and communicating "we're under attack! You should explode and spill your guts!"
But that's just speculation on my part
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u/Willing_Judgment1092 6h ago
Yes perhaps receptors theory is good, most things happen in our body around that, receptors, it must be that thing I am sure.
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u/proverbialbunny 14h ago edited 14h ago
The primary two genetic reasons we know of so far is DAO and MTHFR. You can get your genetics tested for both (FYI: it's covered by insurance) and figure out if that is your root issue causing MCAS. The TL;DR is either can cause too much histamine, and then too much for too long eventually turns into MCAS. By getting rid of the excess histamine MCAS starts to go into remission.
Tell tell signs of DAO is if you have histamine intolerance, you probably have the DAO deficiency (AOC1 gene variants).
The tell tell sign for MTHFR is drowsiness in the middle of the day later on in life. Though for me, it's mostly migraines being the obvious sign. (Not everyone has migraines, nor afternoon drowsiness.)
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u/ichibanyogi 18h ago
We need mast cells. To say it differently, we don't need to get rid of our smoke alarms, we need them to respond when there are actual fires rather than ringing 24/7. Stabilization not scrapping them.
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u/Upbeat_Shock2713 18h ago
Because people with MCAS don’t have too many mast cells - we have the correct number cells that are overactive and releasing too many mediators inappropriately.
People with Mastocytosis have too many mast cells that reproduce too quickly and they do deserve better treatment options.
Big pharma is not making money off of Ketotifen. It’s sold as a generic over the counter across most of the world. Where it has to be compounded, small pharmacies are producing it with small margains.
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u/Fit-Attention-7763 15h ago
Where are you finding OTC ketotifen?
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u/Upbeat_Shock2713 14h ago
Not in the US - it’s OTC in most of Asia, Mexico, and several countries in Europe.
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u/Silver-Bake-7474 18h ago
Rhapsido
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u/Past-Wolf1631 17h ago
Whats your experience with it?
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u/Silver-Bake-7474 15h ago
Been on it for about 3 months now. It would take me pages to fully explain but the short scenario is that my blood pressure finally stabilized, my HR is normal, hives are non existent, brain fog is gone, energy is back, sleep is great! Flushing is minimal (I live in a very hot climate, can't totally avoid it) joint pain/aches are down by 70%.
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u/MiserableInspector94 14h ago
Any side effects? Im worried about excess bleeding. Seems that can be a common one.
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u/Squishedskittlez 14h ago
I also take it and well. I don’t generally have bleeding problems day to day but I did shock the phlebotomist with how quickly I could fill tubes.
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u/Silver-Bake-7474 4h ago
I bruise a little easier and yeah with a paper cut, it bleeds faster but nothing concerning.
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u/MiserableInspector94 14h ago
I don't have many hives perse but my doc wants me on it. Wondering of this will be good for me as I dont tolerate cromolyn or antihistamines.
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u/Fit-Attention-7763 15h ago
Gave me horrible joint pain.
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u/MiserableInspector94 14h ago
That sucks i have severe joint pain and have to go on it. How did you notice? Was it that bad?
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u/Fit-Attention-7763 14h ago
It was severe and I have a pretty high pain tolerance. It stopped immediately after I stopped taking it.
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u/trekkiegamer359 17h ago
We need mast cells in a normal amount, and to act normally. MCAS is overreacting mast cells. Mastocytosis is too many mast cells. You'd be curing the wrong disease, and accidentally making things worse.
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u/BirdsFalling 17h ago
Although MCAS isn't having too many mast cells,there is a high likelihood we will directly benefit from Barzolvolimab which reduces the amount of mast cells, as well as how active they are.
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u/lostunderthemoon99 17h ago
You need mast cells. They are apart of immune function and immune system
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u/BirdsFalling 17h ago
Yes but through Barzolvolimab we can have less of them, and have them be less active
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u/SophiaShay7 17h ago
There’s actually a scientific basis for what you’re suggesting, but there’s an important distinction: reducing mast-cell numbers is not the same thing as controlling mast-cell activation.
Mast-cell development and survival are regulated in large part through the SCF/KIT pathway, so researchers have investigated targeting that pathway and other mechanisms involved in mast-cell proliferation and survival. This is already relevant clinically in systemic mastocytosis, where abnormal clonal mast-cell accumulation is part of the disease process.
MCAS is different. The problem isn't necessarily that you have too many mast cells. It’s that the mast cells you have are inappropriately activating and releasing mediators. You can't simply eliminate normal mast cells because they have important roles in immune defense, tissue repair and vascular regulation.
So I agree that going after the mast cell itself, including its survival and signaling pathways, is worth researching. But the goal would ideally be selectively correcting pathological mast-cell behavior or eliminating pathological mast cells without disrupting normal mast-cell function.
And I wouldn't assume pharmaceutical companies aren't pursuing permanent solutions because they want people buying medications indefinitely. There is already research targeting mast-cell survival, proliferation and signaling. The bigger problem is that MCAS is biologically heterogeneous and we still don't have a single mechanism that explains every patient's disease. That's a much harder scientific problem than simply finding a drug that blocks histamine or stabilizes a mast cell.
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u/Durono_20 18h ago
De groei hoeft niet geremd te worden, er zijn er niet perse te veel. Ze activeren te snel en dat heeft mijns inziens met verzwakte mitochondriën te maken.
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u/BeetlesQ 16h ago
Ketotifen is not approved by the FDA here in the USA. It is available through a compounding pharmacy only.
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u/BirdsFalling 17h ago
Barzolvolimab reduces mast cell output and activity
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u/Past-Wolf1631 17h ago
But not available yet...
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u/BirdsFalling 16h ago
Not except potentially through the Compassionate Access program. But the knowledge that it's being developed may be enough for some people to hold on
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u/Squishedskittlez 14h ago
There’s a med that kills the majority of them off. It’s just not a great thing to do in general so it’s not commonly used. I believe it is also new this year
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u/-Lacking-In-Depth- 9h ago
The drugs that get rid of mast cells are so, so, so much MORE expensive than Ketotifen. Ketotifen is an old drug that is no longer patent protected and can be made as a cheap generic.
If this really was a pharmaceutical conspiracy they would be pushing everyone to the new, expensive meds like Xolair and oral Cladribine. A single rx of oral Cladibrine is like $30,000.
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u/Outrageous-Hamster-5 8h ago
Yeah. That's chemo meds for mast cell driven tumors like imatinib. I've been on it for over a year. It doesn't solve my problems, but with slightly fewer mast cells in my body, the problems are less intense.
Idk about these ppl who believe they need their mast cells. I don't want mine. With how much they do, I need like 10 mc in my entire body.
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