This Is MS Multiple Sclerosis Community: Knowledge & Support

[finn]

Sorry, time to leave the board.

-finn

[billf]

All,
I'm new to the site. This is a great discussion! Should we not be brainstorming about ways to turn our frustrations into actions - actions that can impact the way the NMSS choses to fund, or impact the way that the MS community as a whole views the disease, etc. Obviously, sites like this, and organizations like the Boston Cure Project help that cause. But what more can all of us do? Is it possible to put enough pressure on the NMSS, our neurologists, and drug companies to change their thinking about MS so that we can move away from the fixation with EAE. I think it is! It may take some time, but we should start now. Let's brainstorm about what things all of us in the MS community can do.

[HarryZ]

Bill,

You make some very valid points in the direction we should be proceeding. It is a daunting task because we are up against an established MS medical community that is very powerful with both the written word and even more important, a lot of monetary support.

In the UK there is a LDN Campaign Group that has started a world-wide petition to get clinical trials started on LDN, especially in the UK. I believe they have more than 3000 signatures so far. They have run into some opposition from the UK MS Society but that is to be expected.

I think that we should be focusing our support on organizations such as The Consortium and other MS medical groups that are not influenced by or care about opinions from specialist groups. As well, we should pressing our neurologists and family doctors with information on LDN so that they may start to look into its use.

In the UK the campaign group has contacted the press to give their view of MS and the possibility of using other drugs such as LDN . It would be good if this opportunity came up for other individuals as well. The best way to try and remove false information about LDN or other drugs is to try and educate the people and give them something else to look at other than the standard theories which haven't produced much if anything in the way of MS treatments over the years.

Unfortunately, your suggestion of trying to apply pressure to the NMSS into changing their line of thinking isn't an easy task, if at all even possible. The NMSS is supported by the CRAB drug makers and together they form a very powerful presence in the world of MS medicine. Not even some very prominent MS researchers who are questioning the established theories about MS have been successful at changing their outlook. It's probably best to work around the NMSS for the time being.

Harry

[Guest]

Harry,
thanks for your thoughts, which I agree with for the most part. However, it's hard for me to believe that the the drug companies can continue much longer to ingore some of the emerging truths and continue to invest so much into drugs that are only going to be ~30% effective. That wouldn't be very smart long-term planning on their part. If I was one of their competitors, staying current on some of the emerging truths, I would be looking at developing a drug that did not just emeliorate EAE, but MS in humans - what a blockbuster!. The bottom line is that they cannot coninue to survive in a competitive environment for very long if they are dragging their feet and trying to ignore the latest scientific understandings of MS. Sure, they'll do that for a while, but not indefinitely.
Bill

[willysnout1]

There's a free market for drugs. If a company can develop a drug that works better than the ABCRs and obtain FDA approval, that company will make a lot of money. MS is a big market, which is why there's a lot of activity in the area.

The reason they use EAE is because of the four-stage drug development model required by regulators. The first stage is animal trials. The next three stages are in humans, for safety, efficacy and dosing. If we were to skip the animal trial stage for investigational drugs, it would entail huge risks for people in such trials. Think of the drugs that clear the four stages and still hurt people; could you imagine what would happen if you started the trials with people? Call me insensitive, but I'd rather have a bunch of dead laboratory mice, thank you so much!

Some people might argue that MS is so severe that MSers themselves would be willing to take the risk. I disagree for two reasons. One is ethical; even if MSers were willing to take the risk, is consent produced by desperation really consent? Secondly, the best MS drugs would be those that would catch it early. Could anyone really think they'd populate, much less be able to justify, hugely risky "animal-stage" trials on people whose MS was in its early phase?

EAE is flawed, no doubt. But it's not our enemy. It's a vital tool in allowing any drug development in the MS arena. Beyond that, I don't understand why people would imagine that the drug companies somehow want their drugs to be ineffective against multiple sclerosis. If the ABCRs, or some future substance, were 100% effective but needed to be taken once a day or every 2-3 days or once a week, their sales would increase if their effectiveness was higher.

I have no illusions about the drug companies. I take Avonex and it costs $300 a dose for what I guess is about $15 worth of interferon. There's a lot wrong with the system, but I don't think the EAE model and the basic 4-stage approval process are among the wrongs.

[Daunted]

Thoughtful posts so far...

The four-phase model could be subject to modification, no? In the case of the goat serum, they clearly state there is no animal model for their treatment...

And if MS isn't an autoimmune disorder, and inflammation is just a byproduct, then why does that product work, I wonder...since it is claimed to mainly be an anti-inflammatory...?

[willysnout1]

People who know more than I do about the drug trial process can chime in on how they test things that have no animal equivalents. I am assuming, but without certain confidence, that someone at least does some safety testing on animals before they start injecting things into people. Of course if it's an "alternative" then the usual ethical restrictions often don't apply. On the other hand, the usual proof statements are unavailable. It's the wild West in alternative "medicine," with the results to show for it.

[billf]

I'm in favor of the 4-stage approval process, but to continue to use EAE as the model for MS is questionable at this point. Use it as a model for perfiecting remylination techniqes yes, but to use it as a model for developing ways to halt the disease progression is not likely to give us anything better than the ABCR's after years of R&D and trials. So maybe we don't have a better model at this point. Then let's put more money into basic science and not into years and years of developing something that a few percent better than the ABCR. Thankfully, that is what Art Mellor and the BC Project are trying to promote.

[willysnout1]

In 2002, the Boston Cure project raised $295,000. It spent 19% of that on fund-raising, and anoher 33% on administrative costs. Only 38% was spent on program expenses. Link to Boston Cure Project financials.

In 2002, the National Multiple Sclerosis Society raised $168 million. It spent 17% on fundraising and 7% on administration. It spent 82% on programs. Link to NMSS financials.

I am concerned about the proliferation of MS organizations. Each organization has separate fund-raising and administrative expenses that consume money that would otherwise go for programs including research. Because I favor competition in general, I am sympathetic to the idea of an alternative to NMSS when it comes to private funding of research. But I think it's time for the non-NMSS groups to collaborate with each other to minimize overhead expenses, agree on goals and fund them in the most efficient manner.

[finn]

Sorry, time to leave the board.

-finn

[Guest]

EAE is a poor way to prove if a drug is safe and effective in treating MS.

That's not how they use EAE.

EAE is used by the drug companies mainly to find out if it would be a safe investment to test the drug in a clinical trial. Other way would be to treat few individuals with an experimental therapy, and hope that there will be enough hype about its effectiveness to justify (and finance) a proper clinical trial. That is how Daval International dealt with the "Goat Serum".

I could easily be corrected on this, but I'd be surprised if a drug company could simply begin human trials on an unknown substance without first trying it out on animals. I am thinking that the "goat serum" must have previously been shown safe, perhaps in some other application unrelated to a proposed MS treatment?

Even the man behind the "Goat Serum" doesn't exactly seem to know how the drug works in MS. As an unsuccessful HIV drug it probably modifies the immune system, but it doesn't necessary have to have anti-inflammatory properties.

I'm not sure that anyone actually has to know how a drug works for it to be approved, although I would suspect it helps!

Boston Cure Project has developed the "Cure Map", which seems to be a rational - and an innovative - way to collect and use the data gained from different MS-research projects. They are also preparing a tissue and blood bank to be used by MS-researchers. It seems to me that they are not even trying to compete with NMSS.

I'm not sure either. I suppose the question would be whether MS funding is a zero-sum game, i.e., whether money going to Boston Cure or Montel Williams or whoever else has a foundation would otherwise go to the NMSS. That's impossible to say. My point was that fundraising and administration expenses add up, so when I look at all these new entities I want to see how they justify themselves. Maybe Boston Cure has such a justification, but I also note that they only spend 38% on programs.

So maybe it would be better to compare NMSS with the Canadian MS society. From an European point of view it looks like Canadians are more innovative and less industry dependent than Americans what comes to funding interesting MS-research. It was the Canadian MS society that made it possible to test minocycline in a small clinical trial, and now it is one of the sponsors of the promising MBP8298 trial.

Let's see whether these things bear any fruit. In any case, it would be interesting to read a disciplined and objective critical analysis of the NMSS's priorities and research funding, as opposed to expressions of sentiment and unsubstantiated allegations about their supposed motives.

[Guest]

EAE is a poor way to prove if a drug is safe and effective in treating MS.

That's not how they use EAE.

EAE is used by the drug companies mainly to find out if it would be a safe investment to test the drug in a clinical trial. Other way would be to treat few individuals with an experimental therapy, and hope that there will be enough hype about its effectiveness to justify (and finance) a proper clinical trial. That is how Daval International dealt with the "Goat Serum".

I could easily be corrected on this, but I'd be surprised if a drug company could simply begin human trials on an unknown substance without first trying it out on animals. I am thinking that the "goat serum" must have previously been shown safe, perhaps in some other application unrelated to a proposed MS treatment?

Even the man behind the "Goat Serum" doesn't exactly seem to know how the drug works in MS. As an unsuccessful HIV drug it probably modifies the immune system, but it doesn't necessary have to have anti-inflammatory properties.

I'm not sure that anyone actually has to know how a drug works for it to be approved, although I would suspect it helps!

Boston Cure Project has developed the "Cure Map", which seems to be a rational - and an innovative - way to collect and use the data gained from different MS-research projects. They are also preparing a tissue and blood bank to be used by MS-researchers. It seems to me that they are not even trying to compete with NMSS.

I'm not sure either. I suppose the question would be whether MS funding is a zero-sum game, i.e., whether money going to Boston Cure or Montel Williams or whoever else has a foundation would otherwise go to the NMSS. That's impossible to say. My point was that fundraising and administration expenses add up, so when I look at all these new entities I want to see how they justify themselves. Maybe Boston Cure has such a justification, but I also note that they only spend 38% on programs. Perhaps it's a function of the group being very small, but the 38% number is very low by charity standards.

So maybe it would be better to compare NMSS with the Canadian MS society. From an European point of view it looks like Canadians are more innovative and less industry dependent than Americans what comes to funding interesting MS-research. It was the Canadian MS society that made it possible to test minocycline in a small clinical trial, and now it is one of the sponsors of the promising MBP8298 trial.

Let's see whether these things bear any fruit. In any case, it would be interesting to read a disciplined and objective critical analysis of the NMSS's priorities and research funding, as opposed to expressions of sentiment and unsubstantiated allegations about their supposed motives.

[HarryZ]

Bill,

> However, it's hard for me to believe that the the drug companies can continue much longer to ignore some of the emerging truths and continue to invest so much into drugs that are only going to be ~30% effective.

It these companies were producing drugs for another disease and had this kind of efficacy rate, they would likely have been out of business a long time ago. But they are producing them for MS and the CRABs are the only FDA approved drugs on the market. There is a $ 4 billion world wide market so you only need to do the math and figure out just how much money they are making. And Betaseron and Avonex enjoyed orphan drug status along the way so that helped their profits as well.

So, as long as the money continues to role in and the docs continue to prescribe the CRABs, everyone continues to follow the course. A few years ago a large MS clinic on the west cost of the US got $400.00 for every Betaseron prescription that they issued! Add the support from the docs and you can see how this "money machine" continues to stay in power.

Harry

[HarryZ]

Finn,

According to Dr. P. Behan, Professor of Clinical Neurology, University of Scotland, using the EAE mouse model for human MS research has been an abysmal waste of time. Behan starts off by saying that as a research tool to follow MS in a mouse, the EAE model is great. But he goes on to say that the EAE model of mouse MS is not anything like human MS and that is the main reason why not one treatment that has ever worked in that poor mouse has ever worked in a human.

I think the problem of MS research goes way beyond the mouse. It is a fixation that researchers have had for decades that MS is solely an auto-immune disease and pretty much all research until a couple of years ago has been "locked" into this area. Even dare to suggest that this theory is wrong and other drugs have a more beneficial result will bring down the wrath on you by most MS docs and certainly the NMSS.

Drs. Barnett and Prineas published their work in the Annals of Neurology regarding their findings in autopsies done on brain lesions of MS patients. They found no evidence of the immune system causing the damage. So far, the silence within the MS research world has been incredible. The boat is being rocked and I guess it will be a mater of time to see whether it tips over or continues along the same course.

Harry

[willysnout1]

not one treatment that has ever worked in that poor mouse has ever worked in a human.

Depends on what you call "worked." There's no cure, but there is solid evidence to indicate that the ABCRs delay the progression of MS in a significant percentage of the patients who take them. In any case, what's the alternative to the EAE model?

I think the problem of MS research goes way beyond the mouse. It is a fixation that researchers have had for decades that MS is solely an auto-immune disease and pretty much all research until a couple of years ago has been "locked" into this area. Even dare to suggest that this theory is wrong and other drugs have a more beneficial result will bring down the wrath on you by most MS docs and certainly the NMSS.

What "wrath" are you speaking of? Everywhere I look I see suggestions that MS might be more than one disease and that it might be caused or enhanced by viral infections. Seems to me that if someone has a different hypothesis they ought to get to work testing it and coming up with approaches based on their set of guesses. Proof's in the pudding.

Drs. Barnett and Prineas published their work in the Annals of Neurology regarding their findings in autopsies done on brain lesions of MS patients. They found no evidence of the immune system causing the damage. So far, the silence within the MS research world has been incredible. The boat is being rocked and I guess it will be a mater of time to see whether it tips over or continues along the same course.

What, you expect one article to change everyone's beliefs?

It these companies were producing drugs for another disease and had this kind of efficacy rate, they would likely have been out of business a long time ago.

You mean like the companies that make drugs for cancer that people keep dying of anyway, or the companies that make drugs for AIDS that people keep dying of anyway? Good God, Harry, you need to get used to the fact that at the present time MS is incurable. We'd all like it to change, but it has not changed yet. There are all kinds of incurable diseases out there that are treated with drugs that kinda sorta work. Grow up!

But they are producing them for MS and the CRABs are the only FDA approved drugs on the market. There is a $4 billion world wide market so you only need to do the math and figure out just how much money they are making. And Betaseron and Avonex enjoyed orphan drug status along the way so that helped their profits as well.

Yup, the ABCRs have orphan status. As would any other drugs for MS. There's still lots of dough to be made, wouldn't you say, Harry?

So, as long as the money continues to role in and the docs continue to prescribe the CRABs, everyone continues to follow the course.

That's ridiculous, given that a non-ABCR treatment for MS would also enjoy orphan drug status.

A few years ago a large MS clinic on the west cost of the US got $400.00 for every Betaseron prescription that they issued! Add the support from the docs and you can see how this "money machine" continues to stay in power.

Hey, and I bet the drug companies are putting MS germs in the water. Poisoning our precious bodily fluids, huh Harry?