This Is MS Multiple Sclerosis Community: Knowledge & Support

Whenever I read up on studies and research conducted on MS, I read things like "in a study of 51 patients"..."in a study conducted between 171 males and 191 females with MS"..."in a recent study involving 100 MS patients".......

Why cant more research be done involving large numbers of patients (or a relatively large group)? Surely you wont get any definitive results with a few hundred people, I'm sure of this. I'm also sure that the problem is funding, and if this is so, protests should be made by patients into where the current research funding goes into.

I'm pretty sure that MS patients would first and foremost want research conducted into meds and treatments that halt and reverse symptoms of different severities. I'm also pretty sure that MS patients will also want research into what causes MS in the first place. Like I said, a few hundred people will not give you any insight, and my personal opinion is that these studies with a "handful" of people is money down the drain because nothing is really learned from it.

I am of the firm belief that it is NOT the medical authorities who should dictate where the research goes into, but rather the patients who go through this illness/condition/disease.

I may be totally out of line by saying all of the above, and if I am then please feel free to tell me (but please - without insulting me), so that I know if I am thinking along the right lines or not. But I truly believe that too many neurologists disagree with each other because they surely have the "book knowledge", but they dont have research knowledge but not enough of research is being done.
Thanks. Sorry if I disturbed anyone's thoughts.

You are right on target. Do not even think of apologizing for your comments, because you are revealing the reality of our thinking. I, too, am so revolted by these little studies that always start with the word "may" in them. Of course, then, they suggest further trials are needed. We need a Bill Gates , globally cooperative type endeavor that funds a huge study for the cause of MS. Only then, will a cure be found. The rest is money in the bank for Big Pharm whose bottom line is profit through "management"; another hated word.

Whiteflag,

I can understand your frustration with the slow pace of MS research. I have been following it for some 45 years now. My uncle had MS when I was a teenager and my wife had it for some 35 years before she passed away in 2007.

The reason small numbers of patients are initially used to test a treatment is because the researchers aren't sure if their theory based on lab work is going to be safe and/or anywhere effective with MS patients. You really don't want to have hundreds of patients involved in a study only to find your treatment can be devastating to their health.

My wife was involved in a small clinical trial back in 1997. The drug being tested stopped MS in that poor MS mouse and reversed the symptoms. She was the first patient in Canada to start the trial. I believe there were about 30-40 people enrolled in it. Just about a year into the trial, one patient died from a heart attack that supposedly was caused by the drug. The trial was brought to an immediate halt. My wife, it was learned, was on the placebo.

MS research, until recently, was pretty much geared to using very potent immune system altering drugs. That's because most MS medical people feel that MS is an auto-immune disease. (still not proven after 70 years of research) But drug companies can see huge profits in this kind of treatment, especially if they have obtained orphan status for the drug from the FDA in the US. This status gives the potential treatment all kinds of protection from competition should it get approved for MS treatment.

The research of these drugs have taken the same slow route...theory, safety tests, small clinical trials and then large clinical trials. Time span for his is about 10 years and success is not anywhere near guaranteed. This is why only the drug companies can afford to pay for it although a successful drug will give them profit levels many times over their research costs.

While some alternative treatments have shown promise for MS patients, the results are anecdotal and the people who may develop them don't have the funding required to test them thoroughly.

So what has all of this done for MS patients over the years....provided a high level of frustration with treatments that are minimally effective in the long run.

And today, we don't even have a cause of the disease let alone anything remotely close to a cure.

Harry

Harry - I'm so sorry for the loss of your wife. To think that she was among the first, rather she Was the first, of a new study is not only commendable but really and sincerely - hats off.

I agree with what you and Moom say - its money in the bank for the Big Pharma companies. Its one of my solid beliefs that as long as the big drug companies are actively involved in the research of any disease or condition, there are slim chances of a cure being found. This is, of course, my opinion only.

A rather sick thought, but what do you guys think of this - why are those on death row condemned to die? Why are those who are sentenced for life given the right to live their life? Why can't they be used for for medical testing? I know this is a sickening thought to some, I acknowledge that this goes beyond moral thinking. But someone that the government has condemned to die, or suffer prison for life, why in the world would you not use them for the benefit of those who are alive and battling for their lives with one illness or the other? Is it that these people dont have cancer or a disease? Not possible.

It is the system, it is the system, see my posting of 23 August on
http://www.thisisms.com/ftopic-15323-30.html

And we may draw many more parallels: how telecoms companies filled each others' baskets (came to a halt after a publication in the Financial Times in the late 1980's), in the financial world how the banks filled each others' baskets with loans, credit default swaps etc (came to a halt with the collapse of Lehman Brothers), etc.

And I believe there is even a connection to religion. You will probably say now, this guy has gone completely nuts, but I believe that fasting which comes out of the Old Testament and later was carried forward in all main religions is based on an old folks wisdom, probably based on thousands of years of experience.

I was raised as a catholic. When I was a young child - I am talking now about the 1960's in the Netherlands - we had this yearly period of fasting. And I remember we eat fish, every Friday. I believe that had a religious background as well. Now - it is just a thought - could it be that MS and other diseases as diabetes are rising because of changed cultural habbits and religious patterns?

Fasting raises blood levels of the sugar 2-buten-4-olide. This compound was found to inhibit EAE in Lewis rats.

M. Naiki, et al. 1995. 2-Buten-4-olide (2-B4O) inhibits experimental allergic encephalomyelitis (EAE) in Lewis rats. J Autoimmunity 8(5): 727-739. http://www.ncbi.nlm.nih.gov/pubmed/8579727

Abstract:
Starvation is well known to induce immune suppression. Moreover, the concentration of 2-B4O, an endogenous sugar acid, is elevated in the circulation during starvation. To determine if these events are related, the influence of 2-B4O on experimental allergic encephalomyelitis (EAE) in Lewis rats, a model of human multiple sclerosis (MS), was studied. EAE, characterized by paralysis of hind legs, was induced by immunization with residues 68 to 84 (MB 68-84) of the guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra. Interestingly, the daily administration of 2-B4O intraperitoneally from the day of MB 68-84 immunization (day 0) to day 20 dramatically suppressed the clinical severity of EAE. The daily administration of 2-B4O intraperitoneally from day 0 to day 7 also markedly reduced the clinical symptoms of EAE. In fact, passively induced EAE, using Con A activated spleen cells from rats immunized with MB 68-84 in H37Ra, was also inhibited by daily administration of 2-B4O. Histological examination confirmed clinical findings and revealed that mononuclear cell infiltration into the central nervous system was significantly inhibited by 2-B4O. To clarify the mechanism(s) responsible for suppression of EAE, the effects of 2-B4O on the immune responses to MB 68-84 were examined. When rats were treated daily with 2-B4O for 15 days after immunization with MB 68-84 in H37Ra, the delayed-type hypersensitivity (DTH) response to MB 68-84 was significantly reduced in 2-B4O treated rats as compared with saline treated rats. The proliferative response to MB 68-84 of spleen cells from 2-B4O treated rats was also significantly lower than that of saline treated rats. Our data demonstrate that 2-B4O has the potential to suppress autoimmune responses in both inductive and effector phases. 2-B4O may have significant potential to treat autoimmune diseases.

The chemical structure of 2-buten-4-olide is a 5 member ring with an ester carbonyl conjugated with a carbon-carbon double bond. This would make it an ideal Nrf2 transcription factor activator and potentially put it in the same class of compounds, Nrf2 activators, as Biogen's new drug BG-12. See my prior post at http://www.thisisms.com/forum/post173757.html#p173757.


NHE

and diabetes reversal: http://www.bbc.co.uk/news/health-13887909

co-incidence? of course not, the two - that is MS and diabetes - are linked, see http://www.thisisms.com/ftopic-15188-195.html and following page
and http://www.pnas.org/content/108/suppl.1/4615.full.pdf

Could someone please explain to me why for years people still use the figure of 400,000 when talking about the number of people in the U.S. with MS?

I think if true numbers were given, it would result in a lot more attention, funding and research to this disease.

Personally, I think the number is in the millions. How many people do you know who knows other people with MS, and so on and so on.

M

Yes it's much higher than that but the MS world of medicine doesn't want it to officially go too high. One reason....Orphan Drug status from the FDA. If a drug company wants this status for a drug they are developing or have developed, it gets a lot of protection in patent extensions and other "perks". It greatly reduces the costs for their research/development and in the long run this means more profit. And one condition of Orphan status is the number of people in the US who have the disease can't be too high.

The idea behind it is to encourage drug companies to develop treatments for a disease that doesn't supposedly affect too many people. The company may not see enough profit in a treatment for smaller amounts of patients so if they get cost protection, they are more likely to spend the money and come out with a drug.

Let's just say that the makers of the CRAB$ have done very well over the years.

Harry

Hi!

To concerntrate all funds on medical research and studies in my opinion is a big mistake. Alternatives are just as relevant.

Yes I have been diagnosed as having ms, via a positive MRI, but I havent got it.

I have a misaligned Atlas though which has had knock on effects causing muscle spasm, tremor, l'hermittes, affected my eyesight, blood flow, bladder, these are the symptoms that have either rectified or improved to a bare minimum. But this is just my word for it. I cannot prove it until I walk, and that I do ot doubt.

What is being overlooked by a profession that only seems interested in a drug remedy. They are underestimating the body's ability to heal itself.
Just look at a small cut or graze and watch how remarkably it heals.

I believe thatthe human body is like a precise piece of engineering and has incredible abilities to function, but, as in engineering if one part (i.e. The Atlas in my case) is a fraction out, then it renders the whole system comprimised.

Diagnosis alone has such a psycholical impact and this continues throughout causing a catch 22 with the physical.

The placebo affect will be massive. Say if a drug was tried against a placebo, how could we possible know that the drug itself didnt just have a placebo affect.

I could write a book, but I will now give your probably very sore ears a rest.

And that is basically why I am so passionate about the Atlas theory. This is not an idea that has just popped into my head. Its a gut reaction I have researched in for several years. No I'm not a Dr just an ordinary mum of 3, that received a label of ms, but to me thats all it is.

Fiona

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I do my own research, and find my own answers Its good to talk

Well, on reflection I think they are both right and wrong. Sure, starvation will do something with the immune system. But "suppression" is wrong; I think what really happens is that the immune system calms down. This different viewpoint is very fundamental, is conceptually very important.

Why would it calm down? Because there is something that improves. What? Probably it is the micro-cellular feeding condition. See also this entire thread that is built on this presumption: http://www.thisisms.com/ftopic-15188-210.html

My theory now is very simple: due to starvation, it is the segmented filamentous bacteria that get less room to play. See also the link immediately above. http://www.thisisms.com/ftopic-15188-210.html

You may have missed the point I was trying to make. The blood concentration of 2-buten-4-olide is raised during fasting. This molecule shares the same chemical moiety that it responsible for Nrf2 activation. Nrf2 is a transcription factor which binds to the antioxidant response element regulatory sequence in DNA and activates the transcription of antioxidant enzymes such as heme oxygenase-1, glutathione S-transferase and glutathione peroxidase among others. I suspect that these researchers found 2-buten-4-olide to be helpful in their MS model because of Nrf2 activation. Please see the following papers for a review of Nrf2.

Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway.
Brain. 2011 Mar;134(Pt 3):678-92.

Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals.
Planta Med. 2008 Oct;74(13):1526-39. Epub 2008 Oct 20.

The structure of 2-buten-4-olide can be found here. Click on the "Names and Identifiers" section and then expand to view all synonyms. It call also be found here in this Google Books search result. It's molecule G-5. Scroll up to the prior page to review the structure. Compare this structure to the molecules listed in Fig. 2 of the second paper I've cited above. It has the same moiety consisting of an unsaturated double bond conjugated with a carbonyl group that's responsible for activating the Nrf2 transcription factor. My hypothesis is that the results of the 1995 paper with 2-buten-4-olide in rats can be reinterpreted through the lens of Nrf2 activation.

NHE

@NHE: I am sure starvation does many many things inside the body. I am also sure that the workings of the immune system, the metabolism, the signalling pathways, the neuro messengers etc etc are not even half understood. And for sure, starvation will do something with the 2-buten-4-olide.

But we should not primarily approach the problem -our problem- like this. If we do, we make the same mistake as the neurology and others. Nobody had the oversight, that was completely lost, every body was doing his own little research in his own little corner. They could go on like that for ages without solving anything...

I have seen the same systemic failure happen elsewhere, there are many parallels to draw, this is not unique to the medical sector ...

We should learn from that. We should approach the issue from the meta-level. And then you come to very different conclusions, very powerful as well. The double peak in the graph of the age of onset of MS was the start. And we finished here with an explanation of what is MS.
Please see this page. I am very serious about it, this is what is MS http://www.thisisms.com/ftopic-15188-210.html

I think the focus on starvation, (or "severe calorie restriction"or "therapeutic fasting"), is important because it will make us ask the question, as Leonard has here:
Searching out possible answers may lead to the real mechanism behind the improvement. By the way, my internist has told me that the pancreas stops secreting insulin after three days of fasting.

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My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: http://www.thisisms.com/forum/general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"