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Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. 13 June 2007

Histamine (HA), a biogenic amine with a broad spectrum of activities in both physiological and pathological settings, plays a key regulatory role in experimental allergic encephalomyelitis, the autoimmune model of multiple sclerosis. HA exerts its effect through four G protein-coupled receptors designated HA receptor H1, H2, H3, and H4.
We report here that, compared with wild-type animals, mice with a disrupted HA H3 receptor (H3RKO), the expression of which is normally confined to cells of the nervous system, develop more severe disease and neuroinflammation.

We show that this effect is associated with dysregulation of blood-brain barrier permeability and increased expression of MIP-2, IP-10, and CXCR3 by peripheral T cells.

Our data suggest that pharmacological targeting of the H3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease.

Teuscher C, Subramanian M, Noubade R, Gao JF, Offner H, Zachary JF, Blankenhorn EP.
Departments of Medicine and Pathology, University of Vermont, Burlington, VT 05405


Source Pubmed (13/06/07)

Interesting to note that Elaine Delack, the inventor of Prokarin, wrote articles about the importance of the H2 histamine receptor about 8 years ago. Her hypothesis on why Prokarin helped some MS patients was based on this theory. At that time, there was very little known about the H3 receptor.

Yet the NMSS went out of their way to suppress this information and actually stated they had some research that showed histamine was not beneficial to MS in any way!

How very sad that a treatment, which could possibly help many MS patients' symptoms, was being suppressed by the very organization that tells us how hard they are working to help MS patients around the world!!

Thanks for posting this article, Ian.

Harry

Interesting research.

The more I study, the more I understand why a clear understanding of these inflammatory diseases has been so evasive.

There is just so much involved which covers so many, highly technical fields.

Considering the history, it's hard to be grateful but we are very lucky that researchers seem to be finding interesting and hopeful "workaround" solutions because a clear understanding of the MS disease process seems to be like the carrot on a stick which is always the same distance from our nose regardless of how fast we run towards it.

Bob

Hi Bob,



From my previous note, I guess it all depends on who is doing the research. It would have been interesting to see where histamine research would be today if Dr. Hinton Jonez's work from the early 50's and Elaine's work from the late 90's had been taken seriously!!

Take care.

Harry

Hi Harry,
They say that great minds think alike and there is evidence that minds like yours and mine think alike too

In a situation I've never noticed before, we both hit the "enter" button at 11:01 so at that point it was impossible for me to have seen your previous note.

I only came into the picture about a year ago and I don't know enough about the situation you mention to judge the intentions of the NMSS. I know that people are really nitpicky about situations pertaining to studies and clinical trials and if researchers don't run things exactly by the book, the results aren't taken seriously regardless of the merit of the subject matter.

Do you know of reasons that the NMSS might have found fault with the studies you mention?

It really seems that this isn't the first and won't be the last time in MS research that something valid has been overlooked and that's why I think someone/anyone needs to make a concerted effort to review historical MS research to try to determine what pertinent information might have been discounted as impertinent and might be picked up with the additional knowledge/tools that we have today.

Heck, if they discover that MS isn't autoimmune (which I consider near impossible), you can say "I told you so" and I'll still be smiling because I just want to experience confidence that MS research is on the right track.
Bob

Hi Bob,



Don't think I'll touch that one for the moment...I'll leave the conjecture for the other readers



Years ago I thought highly of the NMSS...until the episode of how they treated Elaine and Prokarin...and boy, did my opinion of them drop off the face of the earth!

Initially, the NMSS didn't like the fact that a tv station in Seattle WA, after pursuing Elaine for weeks, ran an interview with her about Prokarin and some of the very initial good results the docs found when first working with the drug. The NMSS got several calls about Prokarin and at that point, they knew little if anything about it. They didn't like a totally unproven drug being presented to the media and rightly so. But that wasn't Elaine's intention...she relented to the tv station wanting to do the story and figured it would gain only local attention. Well, it certainly went beyond local!!

In the months that followed, Elaine tried to work with the NMSS in possibly introducing Prokarin as a treatment for MS symptoms. She talked to them on the phone and met with them in person. Trials were discussed. But as time went on, it became very apparent that the NMSS had no interest in Prokarin and actually went out of their way to ensure as many road-blocks as possible were put up. They talked ABC news out of doing a report on the results of the Prokarin clinical trial the day The MS Journal made the trial public. I won't bore you with all the details but it was pretty disgusting on how they conducted themselves. And it was the upper executive who was doing this !!

You asked if the NMSS found any fault with the design of the Prokarin clinical trial. Well, three separate university Boards dealing in this kind of trial, approved its design and protocol. The MS Journal, which had a member of the NMSS on its Board of Directors, called the trial "good science" and encouraged further studies with the Prokarin. Yet, one of the first public comments by the NMSS was that the trial design was poor and difficult to follow!!


There are apparently two universities in the US doing research on histamine and it's association with treating MS. The abstract that Ian posted had to do with the H3 receptor. The second university is doing work on the H2 receptor which is the key action in Prokarin. Supposedly the H3 receptor, if over-activated, will cause MS symptoms to become worse but they were working with that poor MS mouse and that can give erroneous results when compared to human MS.

At least they are working in this area and the NMSS has no choice but to be civil with university research behind it. Had they given Elaine the same respect 8 years ago, I'm sure that using histamine to help MS patient symptoms would be much more advanced today. But Elaine was a nurse and didn't have any corporate backing so you can imagine how far those credentials would get her!

Harry

Hi Harry,
I on the other hand started out with a low opinion of the NMSS which elevated when Ian started posting the extensive and diverse list of MS research projects the NMSS funds.

I can't say they're perfect, in fact I highly doubt they're perfect. It definitely sounds like you know what you're talking about and that your argument has merit, but you're referring to something which happened quite a few years ago and the entire Board responsible for the NMSS has probably changed hands by now.

As the largest and oldest MS organization we'd sure better hope that the NMSS has the wherewithal to put the ship in order when situations like what you mentioned happen because their survival depends on donations and they need the MS community behind them.
Bob

Yeah, but,

How much for the Hope?


That is how the NMSS and other organizations survive. Through hope. They keep touting research, and the next big thing. Nothing they bring to table has brought substantial clinical benefit. If they do, strike me down where I stand.

The NMSS is not really that great of an organization, or else they would start making a big deal about Prokarin now, or even minocycline. They post little blurbs about Mino but nothing more. It certainly isn't a miracle drug, but shoot, its probably better than the DMD's. Thats all based of anecdotal evidence, but its just one example. They can't be objective when Big Pharma helps fund them. It won't ever be a level playing field.

People will keep donating, some people donate because they just want to donate to a cause, they don't hold organizations accountable for the progress. Infact, who is? I know they can't gurantee a cure, or an excellent treatment, but after so many years, somethings gotta give.

I personally started out with good thoughts of the NMSS, and I am not impressed anymore. As you can see I am cynical.

Lets see what happens in 2010, lets see if the NMSS Promise stands true. If it does, then the proof is in the pudding. If not, then its just more of the same. Thats my 2 cents anyway...

Brock

Hi Bob,



They really don't have much of a choice in funding this kind of research...they bring in millions and have to disperse this money somewhere. But their admin costs are through the roof and that is the main reason that Montel Williams started his own MS foundation...he states that every penny given to the foundation ends up in research and not in administration costs.



I've only scratched the surface on some of the stories that I learned about the NMSS in the past couple of years. Yes they have some new people in their executive but the problems with Elaine were still taking place only a few years ago. The actions by some of the execs were disgraceful !

Harry

Hi Brock,
I understand your frustration and I'm not sticking up for the NMSS because I really know very little about it although I do know that there are a lot of people involved in the organization, which in itself makes it highly unlikely that there is an organized effort to purposely suppress hopeful research.

What I am saying is that the NMSS is a huge, well known organization which, as you mentioned, lots of people donate to only because it's in the forefront of their minds when they want to donate money.

I guess I'm not sure what people want, the NMSS to straighten their act up? or elimination of the NMSS? I'm not in a position to make judgment on the NMSS but there is no doubt that no matter how poorly the organization is run, it's a great benefit to MS patient in that they are a distribution center which hands the much needed donated money to researchers. Even if we didn't agree with the research they are promoting and funding, all research is advantageous.

Seriously, these recently funded projects seem pretty pertinent and needed to me http://www.nationalmssociety.org/docs/H ... search.pdf

I don't have a strong opinion about the intentions of the people running the NMSS but I think they would have to blatant to the point of illegality before the NMSS could be considered NOT to be a benefit to those with MS.
Bob

Hi Bob,



I mentioned in a previous post that Montel Williams was so upset at seeing the administrative costs of the NMSS that he refused to raise another dime for them but instead started his own foundation.

Here is but one example of waste for a non-profit organization. A couple of years ago Elaine had a meeting with some executives of the NMSS at their Manhattan office. This office is located in a large tower and pretty much covers the entire floor. As Elaine was lead to the meeting room, she noticed that the place was virtually empty and asked where everyone was. She was told that the staff had an education seminar going on and that it was being held at one of the poshy downtown hotels!! You can imagine what that would have cost the NMSS and ask the question as to why that kind of money was being spent while your own facility was vacant!! It's this kind of incident that made Montel give up on the NMSS.

I'm not saying that the NMSS should be closed down but there has to be some better accountability of spending. I guess one of the easiest things in the world to do is spend someone else's money, especially if it makes your life more comfortable


Harry

HarryZ,

Completely agree with you.

Brock

Hi Harry and Brock,
That's exactly my point. That research money is desperately needed and regardless of problems in the NMSS, a large and established organization is going to pull in and dish out a lot more donations than a smaller one.

I'm not trying to make excuses for the NMSS and I'm not even familiar with the situation firsthand but for better or worse, I'd rather try to survive on the money that falls out of a dishonest rich man's pocket than that which falls out of an honest poor man's.

Bob

The latest issue of Inside MS just arrived. It does not lead me to positive comments on this thread. Although the purported emphasis is on "all" the research the society is sponsoring, I found nothing that is searching for the cause of MS. I still believe that the disease and its cause must be understood before an effective treatment can be developed!

Hi Bob,



What did Einstein say once...the definition of stupidity is doing the same thing, time and time again and hoping for a different result.

I look at the NMSS and how they do business and feel this quote can certainly apply to them. It's been more than 40 years since I started following MS research and the course of action in finding the answer to this dreaded disease really hasn't changed very much during this time.

Perhaps that's why we still don't have a clue what the root cause of the disease may be. The major focus has been the use of drugs which do little if anything to help the patient but bring in a lot of revenue that blackens the bottom line of many companies.

I think that I share Lyndacarol's comment about the concern of seeing little emphasis on the "cause"!

Take care.

Harry