This Is MS Multiple Sclerosis Community: Knowledge & Support

I thought I'd go ahead and start a thread to elicit suggestions to the NMSS. Now is our chance. The NMSS has just appointed a new CEO, and they are about to announce their new VP of Research.

If we want to affect changes, the best time is when influential people have just been appointed to their positions and they are eager to MAKE changes!

So, post your suggestions, and believe me, I will make certain they get directly to the NMSS Research Department at the headquarters in New York.

Thanks.

Deb

EDIT: As a matter of fact, I have just alerted the NMSS that I have done this, and IF I get any suggestions posted to this site, I will be forwarding those suggestions to them and would appreciate their response(s).

Come on, what do you have to lose?

SECOND EDIT: As an update, the NMSS has responded to me regarding this, and said yes, they will be interested in our responses (once I have gathered them all together). Anyone?

OddDuck

As you know my pet interests are:

1) the polyamines and their possible involvement in MS and lupus, especially X-linked
polyamine genes,
and
2) epigenetic changes (not just genetics) of the X chromosome and the X inactivation
process, possibly resulting from fragmentation or aberrant replication,
and
3) relating the so-called autoimmune diseases: MS, lupus, RA.

I would be interested in finding out if anyone is considering them and researching them.

I continue to find possible links, such as an article mentioned on BostonCureProject.org this week:
Takeuchi et al. (2005) Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. J Biol Chem paper in press.

To quote them:
'We provide evidence that neuritic beading induced by activated microglia is a feature of neuronal cell dysfunction toward neuronal death, and the neurotoxicity of activated microglia is mediated through N-methyl-D-aspartate (NMDA) receptor signaling.'

Of course I think polyamines are involved, possibly by some increase in their levels: Williams et al. (1991) Modulation of the NMDA receptor by polyamines. Life Sci 48:469-498.

Also, I have been thinking more about bacterial infections and MS. Bacteria secrete putrescine and perhaps spermidine into their surroundings. The MSer's cells could be taking in this local increase. Putrescine and spermidine are the precursors for making spermidine and spermine, respectively. So a local bacterial infection could lead to a local increase in spermine synthesis. This then could lead to the consequences I have mentioned before: blood-brain barrier compromise; modulation of calcium channels; modulation of NMDA receptor signaling; competition with DNA & histone methylation.

As far as the X chromosome and epigenetics, people have looked at skewing of X inactivation with regards to genetics and autoimmunity, with no clear decision. But little if anything has been done about autoimmune diseases and possible loss of dosage compensation (overexpression of X-linked genes) from fragmentation, aberrant replication, and/or improper packaging. I worked in an X inactivation lab so I know something of the current field.

Finally, after my meeting with a big name in polyamines, and finding he had not really been involved in autoimmune disease research (just cancers), it makes me believe that there are few people looking at polyamines and autoimmunity in detail. Seems he would have been contacted more and thereby have more knowledge of the diseases.

Anyway, I would like to find out what the NMSS is doing (if anything) with regards to these areas. I have not seen much in their research summaries. Let me know who you think I should contact. I am fat, dumb, and 'happy' in my cancer research projects (not overpaid though) but if I could get more directly involved in autoimmune research at some point, I would be interested and perhaps willling to make work changes (again).

Wesley

Hi Deb,

Great initiative. Thank you.

When I'm reading about MS, the number of articles linking bacteria’s and virusses to MS astonishes me. For some people, these pathogens seem to have found ways of avoiding the immune system and tricking it into an auto-immune reaction against the body's own cells, mechanisms which have been well documented. Clearly there has to be some truth in it but yet most of the neurological community seems to be able to ignore it.

Knowing this, a clinical trial combining anti-bacterial and anti-viral drugs together with a strategy of supporting and reinforcing the immune system would certainly be worth a try. Don’t you think? I feel that such a clinical trial would not have any difficulties recruiting patients. Now the difficulty is that today’s antibiotics and anti-viral medications might not be potent enough to get rid of enough of these organisms, which in my opinion is the reason most trials using an anti-viral agent alone didn’t achieve significant results, with the exception of interferon, which initially was tested as an anti-viral drug. But I’m sure that some expert neurologists, immunologists and microbiologists (yes, they will have to work together) would come up with an effective treatment strategy.

I was quite happy about the recent success of the potent antibiotic minocycline in a clinical trial achieving a reduction of 84% in enhancing lesions in only a few months time. You can read the full story at the following link: http://www.mssociety.ca/en/research/medmmo-minocycline-june04.htm. But what really makes me quite angry (and that doesn’t happen a lot) is reading that the follow-up trial will compare Copaxone + Minocycline versus Copaxone alone. Why not also comparing it to Minocycline alone? Believe me when I say that some company jumped on this success to promote their own product at the cost of good research and therefore at the cost of the MS patients. Why aren’t our MS societies doing something about that???

I hope our voices will be heard.

Best wishes to all,


PS. Maybe we should launch a survey about this?

Hi, Wesley and HappyDaddy:

Great posts. I will be submitting them.

Ok....Wesley, you asked a question to me regarding who to contact regarding your type of research. Remember, the NMSS only looks at and approves applications for research grants. If one is not submitted to them regarding polyamines, etc., there is not much they can do. They have to have an application for funds in order to approve the funds and get such research started. I might suggest that you look up some MS researchers who are doing genetic research (such as Dr. David Hafler) and inquire with them regarding job positions. Remember, the NMSS does not "do" research themselves. They are an administrative and financial organization that only affiliates with and assists MS researchers. Check out their descriptions of the different types of grants they offer and see if you alone fit the criteria for applying for a research grant yourself! As for your post in total, I will submit it to them as written (I have mentioned you before to them), and have ALREADY alerted them that a specific response would be greatly appreciated.

HappyDaddy:

Well, the problem with the studies you are referring to, is a little complex. Although the NMSS (and like organizations) do have a little political influence (mainly legislative, though), getting involved or influencing a pharmaceutical company's clinical trials (which is what the study you are referring to is. It is being conducted by Teva.), not only presents a conflict of interest legally for a non-profit organization, but since they provide no funding toward such studies done by for-profit corporations (again, not legal), there would not be much "gain" in attempting to interfere with them. This is where we as MSers come in. We can influence, though, where the NMSS's funding is directed, IF the NMSS receives a request from a researcher to perform the type of study you would like to see done. If they receive no applications from researchers for funding for such a study, they cannot directly "initiate" by themselves that such a study be done. They can do an initiative indirectly.........i.e. posting that funds are available for research on "regeneration of the nervous system" or "immune regulation", etc., which is what they do post on their website.

Ok, we all do know that subtle "politics" do go on behind the scenes anywhere, but that has to be delicately handled by a non-profit.

Again, though, letting the NMSS know that if such a study as you suggest were to be submitted for grant funding, that we MSers would like to see them APPROVE funding for such a study, then definitely yes..........they will take that suggestion. In the meantime, if we MSers also encourage our doctors and any other researchers we might know of or come into contact with (and don't let up) to PLEASE apply for grant funds and here's the research we want them to do for us, THAT tactic will go a long way toward us getting what we want. I want to reiterate again, though, as I've done in another thread, we also want to be sure that enough substantive material goes along with our requests for research studies. A researcher and consultant with knowledge of the "jargon" who is AGAINST our particular suggestions, may be able to negate our simple "wishes". We also need to be armed not only with suggestions, but fairly valid substantive reasons or hypotheses for such a study being approved. I know it's hard to combat a medical researcher, but it can be done. I've done it myself. OR in the alternative, we need the "numbers".......i.e. an overwhelming show of MSers (via letters or something) who want the study done (i.e. approved by them)! Period.

And these types of suggestions, etc. are EXACTLY what the NMSS wants to hear about from us. Otherwise, they will appropriate funds based on other factors for our benefit. They need to hear from us. Which is what I'm gonna do!

Keep the posts coming!

Deb

I looked at the NMSS site. At some point I might could qualify for a pilot grant since I can be a PI and my ideas would not have any preliminary data yet. I would probably have to get some special waiver from my institution to let me go for a grant other than cancer-related.

I can certainly think of many projects but I would have to define something practical, pertinent, and doable in the time-frame and funding limits. I'll have to burn some brain cells on it to think of the best project once I get these cancer grants submitted. Don't want to overextend myself either.

One thing that bothered me looking at some of the targeted research projects related to gender differences: most of them were with regards to hormones. It appears to me that the projects on gender differences should be alot broader than just hormones. Certainly chromosomes and X-linked genes should be covered somehow.

Wesley,

Yes, I thought about those same things as you mention (regarding your own personal situation).

As far the gender differences research, I see what you mean. The thing is, apparently what has been mainly applied for and presented by MS researchers as progress in gender differences in MS have been hormonal differences.

When you mention chromosomes and genes like that, that is categorized under "genetic research" and not gender differences. They may "touch" upon a reason why there may be gender differences during genetic research, but you're correct. Are the two areas of research combined into one like you suggest? No. Not at this time. They are still separate issues of study for the most part.

So far, until somebody makes a direct connection between the two (as apparently no MS researcher has found as of yet or has "pushed" as of yet), there would be no reason to create a separate "category" for such a study.

Make the connection which provides viable substantiation that such a "link" between genetics and gender differences in MS exists, and either you or some other researcher apply for the grant, and it might get through. Up until now, it appears you are correct. Apparently nobody has found a connection (in MS that is) or has presented an application for a grant that justifies approving funding for further research in that particular area. At least none that the NMSS has examined.

Start at the top.............contact Dr. David Hafler. See if he'll give you feedback.

Deb

Wesley,

WAIT! There IS somebody researching genetics and gender differences in MS. The NMSS gave funding (a LARGE grant) in October, 2004, to:

Elizabeth P. Blankenhorn, PhD
Drexel University
Philadelphia, PA
NMSS Area: Greater Delaware Valley Chapter
Award: Research Grant
Term/Amount: 10/1/04-9/30/08; $783,134

“Genetic basis for gender differences in
EAE susceptibility” Identifying genes that
may be responsible for differences in the susceptibility
of male and female mice to MSlike
disease, for clues to human MS genes.
There are differences in the way that men
and women experience MS which may hold
clues to its cause. For example, women are
more susceptible to getting MS, and when
men do develop MS the disease tends to be
more progressive. Currently it is not clear
whether these gender differences are the result
of sex hormones, genetics or both. Elizabeth
Blankenhorn, PhD, has been exploring
these questions and is now taking a unique
approach to try to separate the influences of
genes versus hormones in mice with the MSlike
disease EAE.
There are different genetic strains of mice
that have different degrees of susceptibility
to EAE, and they also show gender differences.
By cross-breeding different strains
and deleting specific genes such as those that
control sex hormones, Dr. Blankenhorn
hopes to systematically tease out and identify
genes that are responsible for gender differences.
Because of the similarities between
the genetic material of mice and humans, the
genes identified through this study will be
directly testable in terms of their possible involvement
in human MS.

Well, I guess I was correct then, when I speculated above that if somebody made a viable connection and applied for a grant, that the NMSS would give it! They DID give it!

Deb

EDIT: Contact HER, Wesley! She might listen and be interested. Go to: http://www.drexel.edu/med/microbiology_ ... nhorn.html

Ok....back to further comments and suggestions......... I am compiling them as we go here.

Deb

Ok, folks! We have some initial ANSWERS/RESPONSES from the NMSS Research Department already!

Their comments are highlighted in red, mine are in blue.

First: General comments from the NMSS regarding funding of research:

"The way we describe it is to say that we have a traditional approach and a targeted approach. The traditional approach basically involves the scientific and medical researchers coming to us with their ideas. They submit proposals through our various funding programs and they all compete against each other for the same pool of money. Once we get the proposals we ask specialists in the particular area (i.e. immunologists, clinical trialists etc) to review proposals and then tell us which ones are most worthy of funding. That is how we have approached the funding of research since our inception and is essentially how most funders work."

NOTE FROM DEB: The NMSS also acknowledges that not everyone agrees with the above approach. It may indeed be an imperfect system but seems to work OK, but they specifically say that they are "open to suggestions for a better way."

"About 5 years ago, we did add a new approach in addition to the traditional, and that is called targeted research. In this method we (through the advice of our scientific advisors) identify areas of MS research that can benefit from some additional emphasis. For more background on this visit this page http://www.nationalmssociety.org/Research-Targeted.asp on our web site."

They specifically respond to Wesley's comment regarding what type of research is being done in the area of gender and MS:

"That in fact was one of our first areas for targeting and generated a lot of progress. For that report see this link, http://www.nationalmssociety.org/Resear ... Gender.asp. We also focused on genetics, http://www.nationalmssociety.org/Resear ... netics.asp. We have since turned on to some new areas, such as repairing the nervous system http://www.nationalmssociety.org/Resear ... Repair.asp and pediatric MS, http://www.nationalmssociety.org/Resear ... tedPed.asp)."

It is urged that we review the above information. The NMSS wants us to know that they "are trying to get out in front of new things and to try to accomplish our mission. It is a partnership between us and the Scientific/Medical community. Can we do everything, of course not, but we try to do as much as we can while at the same time making sure that we are investing our precious resources (raised through hard efforts of volunteers like you and others) in the highest quality research that is possible."

Now for specific answers to Wesley and HappyDaddy:

Wesley:

" What I would say to Wesley is that he call or email us! We talk to researchers and potential researchers all the time. They just have to pick up a phone and call (our info is on the web site section on research funding programs) or send an email to the people administering the relevant programs. Based on what I read he is likely eligible to apply to several of our programs. I can’t fix the issue with his Institute’s view of applying to NMSS. "

HappyDaddy:

"With regards to the issue of clinical trials for antibiotics in MS, we are in fact funding a study to look at the underlying biology of how minocycline might modulate disease mechanisms http://www.nationalmssociety.org/Research-Duncan2.asp We have in fact funded some small scale clinical trials in the past looking at the issue in MS. These were early phase trials so nothing definitive has come of them. We (NMSS) can really only fund small initial studies. Large scale clinical trials cost tens of millions which would eat up all of our resources and so we depend on companies to run with these and develop the drugs. Obviously we work with companies when they ask for help, suggestions etc, but it’s a two-way street and we are not always invited in."

I hope this answers some of our initial inquiries. If not, let me know, and I'll pass it on again!

Deb

OddDuck,

The way I see it, I have to get a cancer-related grant for now, based on my situation and basic laziness. That should fund me for a couple of years. And it should move my polyamine ideas forward. We are primarily looking for inhibitors that could work in cancers as well as so-called autoimmune diseases (if the medical world ever grows to accept polyamines as culprits in autoimmune diseases).

With a grant, I can set up the protocols for looking at X inactivation (immunohistochemistry, RNA interference) and for polyamine assays (we are proposing some new protocols for that). I have done immunohistochemistry before elsewhere but a new environment always requires reestablishing the protocols based on the equipment available.

Once I have the grant and protocols are up and running and I get some good preliminary results regarding our hypotheses on cancers (primarily ovarian and breast cancers related to the X chromosome and polyamines), then I can do a seminar on that. The bigwigs would probably come to listen since the ones that count most are interested in breast cancer. (And I have helped their kids on computer projects. Don't you just love nepotism? It's very astute of you to recognize my brown-nosing abilities!)

Then, as part of the seminar, I could mention parallels in so-called autoimmune diseases. Polyamines and disruption of X inactivation: in proliferating cells it leads to cancers, in differentiated cells it leads to apoptosis. In both types there can be autoimmune reactions to the complexes stabilized by elevated polyamine levels. Then I could approach the directors about getting a small NMSS or LFA project related to autoimmune diseases, since I have the protocols running and need more funding. Unfortunately our institute's slogan has 'sole mission is cancer research' in it.

Anyway, it sounds like I have my dance card filled for the rest of my life. But with my 'happy feet', I should be able to fit in another dance or two.

As far as moving to a new position, I'm in Florida for Heaven's sake! Do I want to move back north? Fix the snow and cold problem first. Been there, done that, ad nausem.

Of course the weather down here can be very eradict this time of year: some days it's sunny and in the high 70's, other days it's sunny and in the low 70's. Very unpredictable! (I never get tired of telling that joke to northerns this time of year!)

But, even though my work is now related to cancer, my first interests that got me into research, and still are, are autoimmune diseases.

I still intend to think up the perfect project though related to MS.

Wesley

Wesley,

Ok. I just thought that you wanted to present your ideas to people who were either on your same wavelength (Drexel Univ.) or to the ones who were willing to listen to you now (the NMSS). It doesn't look to me that you need to keep trying to convince so many people who don't want to be convinced in the first place. Wouldn't it be easier to accept the people who ARE and have indicated they HAVE read your ideas and DO want to hear more, instead of working so hard to get someone on your side who isn't?

Why, as a researcher, would YOU just ignore the people who are more likely to take you seriously? And have indicated so. You don't have to be approved for a "grant" in order to make a call and talk to someone.

Now you sound a little like the researchers we ourselves are complaining about. I understand your hesitation about "moving", but you asked the question about that. Besides, it wouldn't take "moving" in order to receive feedback from people who want to listen to your ideas now instead of much later?

Maybe I'm confused as to your goal. I was under the assumption that your initial frustration here was in getting someone to even half-way listen to your theories and believe them. Now you have someone's ear and attention, and suddenly you don't want to take advantage of it?

Deb

EDIT: Besides, Wesley, the NMSS HAS been reading this website including our discussions in prior threads regarding polyamines and gray matter, and believe me, (ask CCMom, even), they would NOT have urged you to apply for a grant with them or to call them to talk (and waste their time or resources) if they didn't think something about your research regarding polyamines, etc. held water or was worth looking into. Are you seeing that fact?

Ok.......come on, folks! Fire away with your questions or suggestions!

We are receiving live personal responses here from the NMSS headquarters in New York, not "form letters". And although you'll have to just trust me on this, the responses are not coming from just a "PR" person, either.

We have them engaged with us right now, so let's take advantage of that fact.

Deb

Deb, you're doing a great thing... thanks for opening up this channel.

_________________
Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

Thanks, Arron!

Actually, I have been remiss.

I want to also publicly thank the Research Department at the NMSS in New York for their graciousness in immediately agreeing to take time out of their extremely busy day to participate "live", as I put it, for a while like this with us!

(I did drop it on them suddenly and out of the blue.) So.........THANKS, New York!



Deb

OddDuck,

Okay, I'll send something by email to NMSS. I don't have the reprints from my article yet but I have a proof copy I could send. It is a .pdf on my computer at work so it will be Monday before I can get it sent. I could also direct them to the discussion on ThisIsMS.com. But I am continually coming across more information to incorporate as I continue to refine the hypothesis, so even that is getting out-dated.

I need to write a cover letter for the email so I'll get that done before Monday. Anything in particular you think I should say? Who should I direct it to there at NMSS?

What I would hope for most is for them to circulate it among some of their research advisors and give me back comments and criticisms. Also, if any of them (or someone else they think of) would be interested in developing a project on some aspect, they could guide me to that person or persons and I could make contact to get into more discussion. Perhaps someone has a graduate student or post-doc looking for a project to do.

What I am doing now is writing grant applications for cancer funding. I really need to focus on it to get it done. Part of our proposal parallels the hypothesis: regarding X-linked polyamine genes. But that is only one way I can see polyamines being a problem in MS (or lupus or cancer). That part of the grant would be front-end work, as you call it, and would be good towards supporting my ideas in cancer and autoimmunity. Also we are proposing back-end work in finding new inhibitors, with some new approaches. I think we have a very strong proposal and have gotten past a preproposal cut-off. So really, if we get the grant, I am in the best place for the next couple of years to work on my ideas, front and back-end. Then perhaps I could either convince the powers-that-be here to let me go for MS or lupus funding, or perhaps I could talk my way into a position somewhere else where I could work on it. A third possibility here is if I can somehow relate it to cancer related autoimmunity. There probably is a connection.

I am wary and sceptical about sending things out, but I am willing to take a chance again. I'll stop my whining and 'Just do it'. (I really did love that Nike slogan).

Wesley