2015: A World without MS Researchers?

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2015: A World without MS Researchers?

Postby bromley » Sat Nov 13, 2004 8:38 am

Dear all,

In mid-October 2004, the UK MS Society held a convention titled '2015: A World without MS?'. Researchers were going to make presentations on how this might happen. I could not attend, but waited for the presentations to be posted on the Society's website. Presentations were posted last week but covered the usual suspects - bladder and bowell problems, fatigue, spasticity, cognition etc, etc. I e-mailed the MS society to find out where the interesting presentations were. They replied:

'The presentations on the theme of future treatments are unfortunately not
available mainly on the request of the speakers. Due to the nature of
the presentation content some speakers were reluctant to have them put
into the public domain- as researchers are very concerned about ideas being stolen'.

Is it me, or do you find this incredible? I assumed researchers were working towards a common goal and would want to exchange ideas etc. What's more annoying is that we are funding them through taxation or charitable donations.

As another year ends, I have noticed that MS researchers have attended MS conferences in Australia, Europe and the US (and no doubt other nice places). Can any of us point to one breakthrough this year in the knowledge on MS that will help us in the future? I know that the usual reason is that MS is very, very complicated - but given the funding provided over the last 50 years, we must expect something more for our money?

Bromley
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Re: 2015: A World without MS Researchers?

Postby Daunted » Sat Nov 13, 2004 1:55 pm

This doesn't surprise me a bit, although it would be mind-blowing if there priority was finding a cure for MS. It obviously isn't. Their priority is profiting from their treatment for MS!!!!

Contrast that with David Wheldon, who posted his theory of ideal antibiotic treatment on the Internet so we could all benefit from the knowledge.
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Re: 2015: A World without MS Researchers?

Postby HarryZ » Sat Nov 13, 2004 6:53 pm

Bromley,

I've been following MS resarch now for over 40 years! When I was a teenager, my uncle had MS and that's when I became interested in the disease.

The comment of finding a cure for MS within 5 years, 10 years or it's "just around the corner" has been going on all this time. And what have we got so far....no proven cause, certainly no cure and nothing really on the horizon that shows a quick resolve to this lousy disease.

I wish I could be more positive on MS research at the moment but as you have seen, the docs don't even want to make public on the net their ideas of what they are looking at. I realize the monetary angle on this is important as well but it continues to sound like the same broken record.

Harry
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Postby BioDocFL » Sat Nov 13, 2004 7:29 pm

There are theories out there in the open, you just need to find them and support them aggressively. Just giving money to an MS organization or the government doesn't mean that the best ideas will be funded. Too often it is the same old worn out theories that get the funding because of politics and the blind faith MSers and MS organizations put in the big name researchers. Once money has been given to the MS organizations or government, you have no control over it so you shouldn't expect to get feedback on research unless you figure out how to make the researchers and organizations accountable to you. Get aggressive. Find out what a particular project is supposed to study in the time frame of the grant and check if it is on track and still focused. If a grant is supposed to support the education and advancement of younger researchers entering the field, you should certainly check that the young researchers are getting papers published and establishing their careers in MS. If a lab isn't publishing and is not advancing the younger researchers' careers, that should raise red flags. Contact post-docs who are in or have been in the labs and get their opinion on the quality of the work being done in the lab. Also, find out if the post-docs and graduate students are coming up with new ideas to study on MS, are they just clones of the mentor, or are they getting out of MS research as soon as they can.
Playing the Devil's advocate though, what's wrong with being motivated by money and possible fame? The drug companies are accountable to their shareholders first. That puts money as a priority and a motivator. Altruism doesn't pay for the shareholders' retirements, so think of it as a balancing act between MSers and retirees. The researchers are trying to find treatments, maybe even cures, but they have lives to live too. Think back to before you found out you or someone close had MS. How concerned were you in finding a cure for MS? Enough to get into a research career on MS? Probably not.
Sorry to sound so cold but that's the way I see it. There are people who are dedicated to helping MSers and aren't motivated by money. But MSers need to figure out how to aggressively push the best ideas forward, motivating both the altruists and the capitalists.
I do think that alot of progress will be made by 2015. It may not come directly from MS projects, but from research on other diseases: neurological, autoimmune, and cancers. It may not be a complete cure but it will probably be better directed treatments based on knowing the causes of MS. I am surprised by how little discussion there is in forums and meetings about the causes of MS compared to the abundant discussion of symptoms and treatments. What discussion there is about the causes does not do a thorough job of relating the theories to the known aspects of MS: female predominance, lesions appearing before inflammation, adult onset typically, blood-brain barrier compromise, etc.
So, what I am suggesting is:
1. Get aggressive and vocal in following specific projects and researchers that are funded by MS organizations.
2. Seek out new ideas as to the causes of MS and have deep discussions in the forums on them so that you understand the ideas and can judge for yourself where the strengths and weaknesses and unanswered questions lay for a particular theory. Educate yourself if you don't understand parts of the theory.
That's my two cents worth.
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Postby dignan » Sat Nov 13, 2004 8:32 pm

I'm no expert, but here is a sample of some of the items I've found in the past few months that I think represent significant progress in MS research. Disclosure seems to be a big deal around here lately, so I freely admit that I am passionately attached to my hope that MS will be cured soon.



New Perspectives in the Fight Against Autoimmunity

Monday August 23, 10:52 am ET - PRNewswire - The September issue of Nature Immunology reports that researchers at Roche Basel in collaboration with immunologists at the Harvard Medical School, Boston, MA, have discovered a naturally occurring peptide that could play a pivotal role in the fight against autoimmune diseases. The so called CLIP (class II associated invariant chain peptide) peptide lowers the production of those cells of the immune system that are critical in triggering pro-inflammatory immune responses, including autoimmunity. This finding may give rise to new therapeutic strategies in particular in the field of rheumatoid arthritis (RA).

http://biz.yahoo.com/prnews/040823/nym102_1.html


Protein may help understand link between infection and cancer

2004/08/26 - Researchers at the BC Cancer Agency are investigating the activity of a protein they discovered in 1996 which regulates how we respond to microbial infections and inflammation-inducing agents. As described in a paper just published in the prestigious journal, Immunity, lead author Dr. Laura Sly has found that this protein – called SHIP (for Src homology 2-containing inositol 5'-phosphatase) – ensures that the body's macrophages and mast cells do not overreact to inflammation-inducing conditions.

This research, explains BC Cancer Agency senior scientist Dr. Gerald Krystal (the senior author on the paper) has important implications not only for cancer control, but increases our understanding of allergies and auto-immune disorders such as asthma, and could play an important role in controlling septic shock in hospital patients.

http://www.bccancer.bc.ca/ABCCA/New...+and+cancer.htm


Jolting system may be what autoimmune patients need to counter chronic effects

BY LAURA BEIL - The Dallas Morning News - DALLAS - (KRT) - The brain and the immune system are at times like members of a dysfunctional family. Sure, they're close. They depend on each other. But under stress, one can drive the other to self-destruction.

Perhaps few people feel this more than the millions who already have a love-hate relationship with their immune systems. People who suffer from any of a host of autoimmune diseases – rheumatoid arthritis, multiple sclerosis or psoriasis, to name a few – can feel the pressures of stress literally in their every move.

Scientists who study the interplay between the brain and immune system are trying to help people with autoimmune conditions buffer themselves from the mental backlash of daily life by studying the effects of proper rest, stress management and other coping strategies. And one idea may be surprising: Fighting stress with stress.

"The key to chronic stress is acute stress," says Dr. Andrew Miller of Emory University School of Medicine. He believes that short bursts of benign stress - a scary movie, say - may actually be good for you.


cientists at UCSB make important discoverythat increases understanding of multiple sclerosis

September 14, 2004 - Scientists at the University of California, Santa Barbara have made an important discovery that will increase the understanding of multiple sclerosis, a debilitating disease of the central nervous system in which the myelin sheath, an insulating membrane surrounding the nerve cells in the brain and spinal cord, start to unravel for reasons as yet unknown.

In a paper appearing in today's issue (Sept. 14) of the Proceedings of the National Academy of Science, several UC Santa Barbara researchers describe the results of a study that shows why the unraveling occurs.

http://www.eurekalert.org/pub_relea...--sau091404.php
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LI researchers find brain, immune system link

BY JAMIE TALAN - STAFF WRITER - September 23, 2004 - Long Island scientists have discovered a direct connection between the brain and the immune system, a finding that could have implications for many diseases.

Until recently, scientists believed the brain interacted with the immune system only indirectly by releasing chemicals into the bloodstream.

But Dr. Kevin Tracey, a professor and head of the center for patient-oriented research at the North Shore-Long Island Jewish Research Institute in Manhasset, found that the vagus nerve, in the brain stem, talks directly to the immune system, which is spread throughout the body.

Once this relationship is understood, Tracey said, it could open a way to prevent immune diseases by altering brain responses, or to treat diseases by tweaking the immune system so that it does not over-respond causing inflammation.

here's the link if you want to read the whole article:
http://www.newsday.com/news/health/...y-top-headlines
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BYU scientists contribute to immune discovery

By Lois M. Collins
Deseret Morning News

Brigham Young University scientists are on an international team that has figured out how the body regulates its immune response.

That may unlock doors to prevent or treat autoimmune illnesses like lupus, multiple sclerosis and rheumatoid arthritis. And it could help explain how the body rallies to fight invaders like viruses, bacteria and even cancer.

http://deseretnews.com/dn/view/0,1249,595104911,00.html
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Postby art » Sun Nov 14, 2004 1:08 pm

While I agree with BioDocFL that if you are going to fund something, do your own research and fund selectively, I have to point out the obvious:

We've been doing research basically the same way since the NMSS started and the money put into MS research has resulted in practically nothing that concretely benefits people with MS (*I'll say more on this below). While these same methods have made some progress in other diseases (always single cause diseases like a single gene, pathogen, toxic agent, etc.), MS is not yielding to them. Other complex diseases are in the same boat.

As a rational approach, wouldn't it make sense to take stock of where we are and try a different tack? This one isn't working. The analogy I have in my mind is that we have 1000's of carpenters (the MS researchers) who can build wonderful houses. But MS needs us to build a skyscraper. But the response of the current system is to give the carpenters more money to build more houses, hoping that some unnamed person or group will suddenly construct a skyscraper out of the houses.

Why don't we use the skills the carpenters have developed to figure out how to build skyscrapers? It will take a different funding structure and different management structure but we have developed the basic skills to get started - we just need to use them differently, develop new ones, and include a more diverse set of disciplines to produce different results. Tackling complex diseases requires a different approach and just throwing more money at the old approach won't fix that.

It's not that researchers have been doing the wrong things all the time. This sort of "house building" has worked in other diseases, but I think we have enough evidence to say it isn't working in MS. Let's be intelligent and stop banging our heads against the wall and use what we've learned to create a battering ram. Perhaps a cure *is* just around the corner, just not the corner we've been hanging out on.

* OK, why do I say we haven't gotten anthing out of MS research today? I'm talking about things that dramatically affect my disease today - which I think includes the ABCR's, Novantrone, and MRIs.

AB&R are interferons, developed not for MS, but cancer and tried in MS later. That's great, but it wasn't MS research that brought that about and getting them to market was an amazing battle fought by Larry Jacobs that seriously threatened his career at times. Copaxone came out of MS research, but in my opinion the wrong way - it was designed to *cause* MS in animals so we would have a better model. Shows how much we understand about MS. Novantrone is another cancer drug, not developed for MS. We can't even say how these drugs do what they do in any deeply understood way. MRI is wonderful, but wasn't developed for MS either.

While serendipity is a great thing, and I'm glad it happens, I don't feel comfortable depending on it for producing a cure. I'd like to see some impact on MS come out of having a concrete understanding of the disease - that's when I'll call it progress rather than serendipity. Serendipity will continue to happen even if we are working towards concrete goals. Really!

Antegren may the first such product. It is a drug designed to have a specific effect based on a specific hypothesis of how the disease operates and has been demonstrated to have the designed effect and recent published results appear to support that it affects the disease. But look where that came from - not the main sources of public funding for MS research, but a pharma company.
Art Mellor Dx 2000
You can see what we have to offer at
http://www.acceleratedcure.org/offerings/
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Postby HarryZ » Sun Nov 14, 2004 5:50 pm

Art,

You certainly have touched upon many significant points and they all make sense to me. And you are so right about what we have seen coming from every direction except grass roots MS research. Unfortunately MS research has been fixated with the immune system theory for decades and no matter who comes by with another theory, it gets shot down immediately and quickly.

I can speak of one drug, Prokarin, which my wife has been taking for 4 1/2 years and doing as well as anyone with SPMS can possibly do. Now the theory behind how this drug works is totally different than the standard immune system belief. When it first appeared about 5 years ago, you would have thought that the NMSS would have shown some inkling of encouragement at perhaps giving it a second look. Not on your life!! They went all out to ensure it got nowhere. There's quite a story behind it but it is but one example of what you posted about past MS research over the years.

Harry
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Postby BioDocFL » Sun Nov 14, 2004 5:57 pm

I think Art and I are saying the same thing, "How many immunologists does it take to build a skyscraper? None, because they are all working on getting their retirement houses built and paid for." Something like that, never could follow analogies well. Seriously though, if MS is not initially an immunological problem (inflammation) but rather a neurological problem (demyelination and lesions), then perhaps it is more a problem for neurologists to solve rather than immunologists.
I see what Art is saying, that larger collaborations are needed to address these difficult diseases. And that they should be focused on specific, pertinent questions in defined projects and I would add, with specific timeframes and bringing in new technologies and theories. That is what the NIH has realized in the past 10 years. Since roughly less than 20% of grant applications get funded, those that bring together a group of labs at different sites with different techniques to address a specific problem will have a better chance of getting funded, versus a single investigator working solo. The single investigator with a lab focused on one technique might have worked circa 1980's but now there is too much new technology that can be brought to bear on a problem so a grant application should bring together several approaches and the expertise of several labs. That is what I am involved in with regards to cancer research. But, as I have said before, the enzymes that I am studying I believe are also involved in autoimmune diseases. I should explain the collaborative project with which I am involved and it will give you an idea of what is probably needed for MS.
I work on molecular modeling of enzymes to find inhibitors to those enzymes. In particular, we are looking at polyamine enzymes. I believe polyamines are involved in several of the autoimmune diseases as well as cancers in a causative role (see the ThisIsMS.com forum: general discussion > polyamines). I create a computer model of an enzyme and then run docking experiments on the computer where 100,000s of small molecular structures (we have over 1.5 million to try) are fitted one at a time into the active site of the enzyme in different orientations to see how they fit. This is in silico (in computer) virtual screening. A docking score is obtained for each small molecule. We then take the top 100 or so and discuss them with our collaborators. The collaborators (who are at different institutions) will buy the top compounds (or synthesize them if need be) and then test the compounds in actual enzyme assays. The compounds that show good inhibition of the enzyme will be studied further. We take the basic structure of a top compound and again, using the computer, generate new variations of the compound by running a program that changes side groups of atoms on the compound to generate similar but new structures that still fit in the active site. These are then evaluated and tested to see if they dock better and inhibit the enzyme better. We can also run ADMET testing on the computer, saving time by avoiding testing of toxic or ineffective compounds. ADMET = Adsorption, Distribution, Metabolism, Elimination, and Toxicity. The leading candidate compounds are tested in tissue cultures of human cells and then in mice. Eventually they will get into clinical trials. The lead compounds we have found so far have better docking scores than the known inhibitors of the enzymes so our results at this early stage (less than a year on the project) are encouraging. Our collaborators are some of the top labs in the world with regards to these enzymes and the synthesis and testing that is needed. But we are also working to get more funding so that we can add some newer technologies to our project, such as RNA interference and high throughput screening.
I have proposed a hypothesis relating polyamines to MS. It would be great if NMSS or other funding organizations were interested in the hypothesis. I would also like to see how Art fits the hypothesis into his Boston Cure Project map. I do not see polyamines or chromosome fragmentation or quaking or jimpy mice discussed much with regards to MS. I gave a far more detailed explanation of the hypothesis relative to MS characteristics than any other hypothesis out there.
I do not know anyone personally who has MS or lupus, so I have no personal stake in this. In fact, it has cost me more being interested in them than if I had not gotten interested. Now, I am more concerned with cancers by necessity in order to stay at the front of research with my ideas. I would really like to see research on 'autoimmune' diseases attain a new paradigm because I think that is needed. And, I would like to see MSers give more concern to finding the causes of MS. I am at a cancer center and research institute. The patients are perhaps more inspiring than what I have seen with autoimmune patients. The cancer patients are of course in more of a life/death struggle and therefore get more active (or resigned) in their fate. Their ordeals are relatively more acute, intense, and perhaps final. The cancer research groups seem to have more focus and excitement. When I was around immunological research before, there didn't seem to be the immediacy or focus or relevancy needed, or interest in new ideas. Just think of how long it takes to get a definitive diagnosis of an autoimmune disease versus a cancer. Of course you could say that differential diagnosis of autoimmune diseases is more difficult due to overlap of symptoms but that suggests that there are similarities in cause that should be researched. Anyway, I think we all want the same things, cures for each of these diseases.
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Postby OddDuck » Sun Nov 14, 2004 6:03 pm

Hi, Wesley!

I see what Art is saying, that larger collaborations are needed to address these difficult diseases. And that they should be focused on specific, pertinent questions in defined projects and I would add, with specific timeframes and bringing in new technologies and theories.


and

Since roughly less than 20% of grant applications get funded, those that bring together a group of labs at different sites with different techniques to address a specific problem will have a better chance of getting funded, versus a single investigator working solo.


I just had to chime in and say I couldn't agree more!

Deb

EDIT: Sorry, I just realized I must have missed this statement below, too, and again, even though it's probably not a useful comment by any means, I wanted to say "Isn't THAT the truth!" That's one of my pet peeves also. No real apparent major advances in diagnostic procedures or products! And/or if and when there is one, the length of time it takes to get it implemented in the field. People stay in "limbo" SO long, it seems. That's SO difficult for a person.

Just think of how long it takes to get a definitive diagnosis of an autoimmune disease versus a cancer.
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Postby BioDocFL » Sun Nov 14, 2004 7:12 pm

Hi OddDuck,

OT: I am working on some additional aspects to my hypothesis: polyamine block of glutamate receptors and polyamine versus serotonin competition for S-adenosylmethionine. I think there is a serotonin/depression link that could have abnormal polyamine synthesis involved. Still got to think out the details more.

But with regards to large collaborative projects on MS, I would like to see some people involved that have not been working on MS before but could be major contributors to new approaches: David Allis on epigenetic marks in chromatin, Rudolf Jaenisch on X chromosome inactivation, and Anthony Pegg on polyamines. They are basic researchers, not so much focused on specific diseases but the type of people you would want to lock in a room until they came up with some serious, well thought out project ideas, figuring that they could do it with their expertise.
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Postby OddDuck » Sun Nov 14, 2004 7:31 pm

I know exactly what you mean (i.e. locking certain folks together).

Hey....truly.....what you mention there regarding glutamate and serotonin, etc. sounds REALLY interesting!!! And I think you (again) might be onto something there, Wesley!

Hey.........keep on it! And as always, keep us posted on your progress!

Deb
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skyscrapers, autoimmunity, and other jive...

Postby RevLeonidas » Mon Dec 06, 2004 3:37 pm

Skyscrapers to autoimmunity need not be built.
Here's a place where MS research should start.

Find subjects (people) with a positive Multiple Sclerosis diagnosis who have shown clinical improvement in disease associated indicators: MRI lesion reduction, EDS improvement, etc. Call these the clinically-improved.

Of these subjects, find similar every-day physical behavioral characteristics regarding details of diet, exercise, and rest.

If such a research effort is conducted using sound methodologies, I suspect that an individualized dietary deficiency will be linked to Multiple Sclerosis. Building skyscrapers of potions, gene therapy, et. al. is time wasted on a cure based on the autoimmunity mess-guess that's only shown to be right part-of-the-time.

I know that the aforementioned clinically-improved subjects exist, because I'm one of them. I'm not "all-better," but I have shown significant, "unexplainable" signs of improvement, and I haven't had any flare-ups. Since my condition has improved, I went looking to see if I was the only one, and I found that I am not.

There are doctors who say that this isn't possible because MS is a progressive disease, and it doesn't fit into their nice little autoimmune, neurological disorder packet; however, there is a group of us out here. People like myself could be an anomaly, but don't you deserve to know if we are?

Time for another paradigm.

Eat better, exercise more,
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share

Postby feesher » Tue Dec 07, 2004 8:20 am

Rev,

Please share your experince.

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Experience?

Postby RevLeonidas » Tue Dec 07, 2004 1:31 pm

Feesher,

Like most all MSers, my experience started well before my diagnosis in 1997, but that's a good year to start since that's the year I started seeing a neurologist for MS. The year 1997 was when I had my first MRI. This was an MRI w/contrast in a "closed" MRI. I had one large lesion on my brainstem, five quarter-size or larger lesions scattered throughout my right hemisphere, and four pea-sized lesions centered and in my left hemisphere.

I went about in the typical misery of weekly Avonex injections, and three to four flare-ups a year (steroids [dexamethasone] at least once a year). I did a typical physiological decline from increased fatigue and general malaise.

Perhaps it is fortunate that my ultimate source of misery is constipation. This was my Everest of this disease, so I tried to find the most effective way to remedy the problem. It is a simple solution. The most effective way to remedy constipation is to cleanse the bowel. The safest, most effective way to cleanse the bowel is by fasting, so I did a little reading on fasting. Historically, it has been an effective medicine since Hippocrates; however, with the advent antibiotic medicine, all the old medical practices, good and bad, were systematically abandoned.

Some of the jive I read on fasting suggests that this age-old medical practice enables a body to heal itself. I have reason to believe this jive: healthful fasting does aid a body to heal itself. I did my first fast January 2002, my overall health has improved ever since. I eat better, I exercise more, I have more energy, all the numbness in my hands and feet has departed, and much of my balance has returned.

In Fall 2003, my neurologist ordered a second set of MRIs; this time, they were taken with an "open" MRI. When I visited my neurologist to review the MRI, and my disease progress, he told me that "we see something with you that we don't usually see, two lesions went away." I suspected that fasting, or a well-planned diet, had something to do with this. For other reasons, I quit taking Avonex soon after.

January 2004, I moved to a different city, started taking LDN, and my health continues to improve. My new neurologist requested that I get another set of MRI's in a "closed" MRI in the fall of 2004. Her contention was that the open MRI missed some of my previously identified lesions; however, instead of showing an increase in lesions, my last MRIs show a further reduction. I no longer have a lesion on my brain stem, there is one medium sized lesion in my right hemisphere, and there are five small, dot-sized lesions around the center. Sorry I don't recall the physiological terms for the brain zones; I was too dumb and lazy to take anatomy in college.

I know there are a lot of loose ends in my story, and there are a lot of different factors which may be contributing to my overall wellness; however, my situation suggests that MRIs and CRAB drugs only work sometimes. Until doctors can realize sometimes isn't the answer we'll be stuck in the autoimmune Tower of Babel.

Be Well,
Rev. Leonidas[/code]
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