"Mast Cells" - and MS, Mast Cell Activation Syndrome and CRPS

Folks,

Rick's Doctor treating him for CPNi, forwarded the following to Rick today.  It appears at the least to support the idea of using an Antihistamine to prevent demyelinationi, and perhaps to help with promoting remyelinationi.  See the last couple of paragraphs of the post (not the articles) for how this might be related to CPN and it's treatment.

Abstract

Multiple sclerosis (MSi) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood–brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseasesi was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.

The above was posted here:

http://onlinelibrary.wiley.com/doi/10.1002/ana.410370112/abstract;jsessi...<

Additional information the good Doctor sent included:

http://www.rsds.org/newsletter/Mast_Cell_Activation_Syndrome_and_CRPS.html<

This is supportive of the idea of adding an antihistamine to assist in speeding up remyelination - and the Doctor has also recently both mentioned the role of Antihistamine for helping Rick and may have reviewed the information I sent him and discussed with him in my recent meeting with him as a new patient to treat CPN.

That information is really mostly from this post:

http://cpnhelp.org/ms_cap_protocol_variation<

I may add this information to that post as well.

So - as to Rick's recent efforts and progress:

It's very early to suggest that his recent (2 weeks) clemastine addition has anything to do with this.  Rick has only just started the clemastine, and only started for the first time in several years - a regular, disciplined and consistent exercise program.  Will power and desire are likely a big part of what we've seen.

That, and an increasingly strong belief that he's no longer fighting a losing battle, e.g. that nothing he could do would make any difference so why bother trying.  I believe his recent efforts are based on that change in outlook he's been increasingly internalizing, and at least partly on the same time-table my confidence has been increasing.  We are very close to or over halfway through his regularly scheduled time of year (January to late March) to have a serious relapse - and - NONE! 

So - he's been working on standing up and down, from his bed or his wheelchair - with a walker and someone to assist, for 2 weeks now.  Yesterday, and for the first time in quite some time - he was able to lift a foot and move it a bit - 3 inches I heard from him and his brother Chris last night.  It's a small "step" - but the first one he's done in some time...

Interesting set of articles above - and more information about how Histamines could play a huge role in at least some cases of MS.  I'm curious about the possibility of CPN playing a role in causing inflammationi in the brain - leading to Mast Cells releasing Histamines and fouling things up for Oligodendrocytes.  Apparently, histamines are part of Mast Cells and easily released.  See the article for more details on that.  Clemastine is a very special Antihistamine given it's other mode of action - e.g. turning the "on-switch" in Olidgodendrocyte Precursor Cells, causing them to mature into Oligodendrocytes and to proliferate through the brain and reymyelinate axons.  Clemastine does that through it's "anti-muscarinic" M3 metabolic pathway.  For those details - see the forum post I mentioned above - and again here: http://cpnhelp.org/ms_cap_protocol_variation. <

I mentioned the last part to be sure the dots are connected for folks as to how this post might relate to the more general subject of CPN treatment and may not be just related to MS.  Another connection that folks may find in the articles - is through Fibromyalgiai sorts of symptoms.

Anyway - all that said....

My Best & Highest Regards to all!

Tom C

Very interesting to read that antihistamines may assist in speeding up remyelinationi!

And awesome to read that Rick has Not relapsed and is able to move his foot!!!

Thanks for posting this great information.

All the best,

Louise_C

03-23-2013 start date
PPMSi  - May 2009, working with Naturopath since 2009, taking listed supplement_s, plus LDNi 4.5 and L-Arginine Plus.
[had CCSVI in 2011 - helped a little]-Doxyi 200 mg, Azithromycin 250 M-W-F & NACi 1000 mg.
Tinidazole #16 - 1000 mg days FEB 20 thru 24 2015

Hi Louise,

To be very specific - yes Antihistamines appear, from this Mast article above, to be helpful in general.  The other forum post, specifically on Clemastine, has information about Clemastine that points to it being perhaps the very best current antihistamine for the purpose of remyelinationi.

To expound briefly, and knowing you may know this anyway, for the benefit of other future readers, clemastine fumarate - aka "Tavist" - the brand name folks may be familiar with, has two modes of action relevant to remyelination:

1. The histamine H1 receptor antagonist pathway - aka "antihistamine" - which the MAST article posted above speaks to and

2. The "anti-muscarinic" pathway.  Apparently, the precursor cells for Oligodendrocytes - the cells that are responsible for remyelination, have a "switch" that is normally turned off.  The muscarinic m3 pathway - is present on the oligodendrocytes and clemastine through that pathway turns on the switch that tells those precursors to mature into oligodendrocytes and to proliferate through the brain where they will hopefully then remyelinate axons.

My apologies if this is at all repetitive.  And - at least on the surface, at least one other antihistmine than clemastine appears to be extremely closely related - benedryl aka diphenhydramine is in the same family, and also appears to have the anti-muscarinic effect.  What's being tested though in a clinical trial - at UCSF - is clemastine.  They also published the doseages being tested for - 8mg a day.  Someone trying benedryl or another antihistamine may not have as much information to go on as is available for clemastine.

One more bit to this - the UCSF phase 2 clinical trial was initiated after a "highly advanced, high speed image based screening method" was used to screen over a thousand different drugs already FDA approved.  8 drugs all stood out - with clemastine showing the most benefit.

So, while clemastine is many times more expensive than benedryl (10x - 50 cents a pill vs. less than a nickel for a benedryl) - we know more about clemastine specifically in this context.  At retail pricing in the US for private labelled versions (Wal-hist for example from walgreens) - and at the full 8mg a day dose - the monthly cost is likely around $150.  Someone on a very tight budget could do a trial of benedryl -- afterall it's used as a sleeping aide for gosh sakes - I suggested Rick go with Clemastine instead for the above reasons.

Again - my apologies for being so thorough - but I think it's important to point out the distinction between antihistamines in general and clemastine as a specific anithistamine with it's very specific ratios of antihistamine and anti-muscarinic effects.

My very Best & Highest Regards to all!

Tom C

Proud Parent of Rick - R started CAPi in Nov. 13. Small measurable improvements as of 7/14, more by 10/14.  Holding Steady in early 2017.  "I will leave no stone unturned, no theory unexamined, to help my son." Tommi

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