The role of the BBB

If it's on your mind and it has to do with multiple sclerosis in any way, post it here.

Postby Rita » Mon Apr 09, 2007 9:59 am

The problem to build a house from the roof going downwards is that is harder and dangerous cause if you are not extremely precise all the building may fall down and you have to start again, this takes you a lot of time and is very expensive.
MS need a good architect and a better team to work in the right way. Even if it is not so fast in the beginning and the business is not so clear, it will be farther on.
I love to read and learn a lot from all of you.
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Postby TonyJegs » Mon Apr 09, 2007 12:59 pm

-finn

1. Yes, they could be of some benefit for aggressive MS with rapid progression, the number of patients with this form is very small, they usually didn’t survive 1,5-2 years.
2. I think it is possible to create an animal model mimic human MS, other question is why it is not in agenda of any current research?
3. MS is a ‘drop in a bucket’ compare Alzheimer Disease.
4. Einstein used pencil and piece of paper. I don’t think that huge team of different specialists will work better, they will never understand each other completely.
5. There are thousands of active compounds involved during damage-repair cycle. I don’t believe that single component could change it much.

-Lyon

You wrote: “Obviously the farther back in the process we can direct treatment, the more favorable the results will be”.
You are absolutely right.
Concerning “threshold leading to the end of MS. It's within sight.”.
Well, It could be, if we stop dealing with EAE treatment and go back to real MS.

Kind regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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Postby Lyon » Mon Apr 09, 2007 1:12 pm

oo
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Postby finn » Tue Apr 10, 2007 4:58 am

Tony,

a couple of quick notes:

TonyJegs wrote:1. Yes, they could be of some benefit for aggressive MS with rapid progression, the number of patients with this form is very small, they usually didn’t survive 1,5-2 years.
Now you got me even more confused. How they would have even been able to measure the effectiveness of a disease modifying drug in a very small subgroup of MS patients who "usually didn't survive 1,5-2 years"?

TonyJegs wrote:2. I think it is possible to create an animal model mimic human MS, other question is why it is not in agenda of any current research?
Actually, it seems to be. And as far as I know, there are already other animal models for MS, but they are not used as often as EAE. What do you think about them?

TonyJegs wrote:3. MS is a ‘drop in a bucket’ compare Alzheimer Disease.
Yes, and Parkinson's disease is much bigger business than MS, too. But still, I think the four billion dollar annual turnover of MS drugs is quite a lot.

TonyJegs wrote:4. Einstein used pencil and piece of paper. I don’t think that huge team of different specialists will work better, they will never understand each other completely.
Well, Einstein was a genious, but it seems like most MS-researchers might not be that smart ;-) Seriously, I'm sure that researchers working as a group could achieve more than the same amount of people working independently.

TonyJegs wrote:5. There are thousands of active compounds involved during damage-repair cycle. I don’t believe that single component could change it much.
I'd say it depends on the component ;-) I personally think the solution might turn out to be much simplier than thought.

Be well.

-finn
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Postby Lyon » Tue Apr 10, 2007 8:35 am

oo
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Postby TonyJegs » Tue Apr 10, 2007 8:43 am

- finn

1. It is easy to track them down nowadays, they will agree to conduct any experimental study because they have nothing to loose. The question is why it didn’t happen? The answer – anti-cancer drugs will work better. Therefore the most applicable (target) group with MS could be eliminated, which is not good for drug ‘reputation’.
Please read my post about ‘16 years of betaseron use’, get some ideas.

2. So far any of current (2007) animal models couldn’t mimic human MS, esp. R-R form which is up to 75-85% of ‘whole’ MS. There are still playing immunity ‘tune’. By doing that they still chasing remote secondary features of MS instead of paying more attention to condition how the very first lesion occurs.

3. Well, it is all relative, the competition is fierce, and believe me they have the same problems with explanation of other neurodegenerative disorders.
Personally I was waiting for one study on Alzheimer for maybe 12 years, and it came recently form Germany, under evaluated of course, but that was good news anyway, because from now it be there forever, and it will be used properly, sooner or later.

4. Every researcher does what he/she trained to do. My point was that lack of global conceptuality disperses the efforts made.
Einstein was mentioned not because I admire him, I am pretty far from that, but he is a ‘well recognized brand”. There is a bunch of other physicists I respect more.

5. Every patient wants to get the ‘magic’ pill, preferably once a day. Unfortunately it doesn’t work this way when you deal with complex problem.

Kind regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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Postby TonyJegs » Tue Apr 10, 2007 9:10 am

- Bob

This is a decent article.

Let me explain this part: “Disadvantages for experimental studies include the unpredictability of lesion location and the variability with time of lesion pathology.”
It is possible to make a model with predictable lesion location, trust me on that. When you understand this mechanism first, you go further and do predictable timing. After that you analyze how to influent reverse.

“When working toward the solution of a problem, it always helps if you know the answer.”
- Rule of Accuracy -

Kind regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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Postby Lyon » Tue Apr 10, 2007 10:17 am

oo
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Postby TonyJegs » Wed Apr 11, 2007 12:18 pm

-Bob

Let’s go back to the article you quoted before.

All mentioned in the article animal models are, of course, not MS-mimic models. Brain damage induced there by variety of factors/agents from ‘outside’, not from ‘inside’ the brain. All these models are good for research on how treat or what’s going on if … (add the agent used for the model creation). Use of these models in MS is limited. More, the results of these experiments are predictable, so they will serve not for ‘discovery’ but for approval of certain type of treatment.

If I were in position to create an animal model of MS, I’ll walk away from rodents. They of course are very convenient for lab use, and there is a huge business on providing labs with specific lines of mice and rats, you will be shocked to learn the price of genetically modified rat with certain knocked-out gene.
By the way, when you consider to do a specific animal model, you must do research on local Ethics Committee, who approves the protocol. They are a big headache, and they could ban everything despite of urgent medical need in this particular experiment. They are perfect example of another (unbelievable) distortion of modern science and medicine.
I remember when one guy came up with a good model of RA, and he couldn’t get approval for 2 years because of “suffering of pain animals”, well, how you could mimic an attack of RA without joint damage?
That could explain why sometimes researchers couldn’t come with more sophisticated animal models for reasons far beyond the science.

Back to MS. My point is that unless more attention will be paid to initial condition of the brain before first lesion appear, where is no autoimmunity yet, all current research will ‘hit nothing’. With all my respect to Myelin Foundation Project, when you analyze what ideas they explore, and what kind of experiments they have launched, well, another curve of the labyrinth will be explored, and what?

Please don’t accept my posts as discouraging ones. I think that increased awareness of current disappointing situation on MS could do the trick and then new ideas will find their way easier and faster.

Sorry, maybe I didn’t answer your question in full, but all subjects on MS are huge.

King regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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Postby Lyon » Wed Apr 11, 2007 12:41 pm

oo
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Postby TonyJegs » Wed Apr 11, 2007 10:42 pm

Hi, Bob

I don't consider alternatives discouraging. What I find discouraging is research continuing exactly as it has in the past even though it's obvious that we aren't making great progress. I think there are some interesting treatment options in the works but that is more the luck of the draw than gain from knowledge. Throw enough chemicals at MS over a long enough period of time and sooner or later the odds will throw you one which shows a little benefit.


Let's aim for higher target - reverse of MS.

Kind regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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Postby Lyon » Thu Apr 12, 2007 6:39 am

oo
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Postby TonyJegs » Thu Apr 12, 2007 8:23 am

Lyon wrote:Not to nit pick but by "reverse of MS" you're referring to a two part process? Stopping the MS disease process and aiding the healing process?
Bob


I don't use an alcohol either, but I drink coffee as well as tea.:)

All 'benign' cases of MS, or cases with 'miraculous' spontaneous recovery, when people get back to normal life, after being bedridden or wheel-chaired for years (and sometimes even without any treatment!), are existent prove that it is possible.

Kind regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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Postby Lyon » Thu Apr 12, 2007 8:59 am

oo
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Postby TonyJegs » Thu Apr 12, 2007 12:11 pm

Hi, Bob

You got my point.

Sharks boom died quietly. I belive that normal scientists didn't buy it from the beginning.

Kind regards,
Tony
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer
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