Lesion load / auto-immune theory

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

Lesion load / auto-immune theory

Postby bromley » Mon Nov 01, 2004 2:43 pm

Dear all,

Many MS treatments refer to the effectiveness they have on reducing the 'lesion load'. In the case of Antegren, the speculation is that the effect might be much higher than current treatments. What does this term mean? Having less lesions (I assume) is a good thing and would result in less damage to the myelin and the underlying nerve cells. I assume that having less lesions would also allow the body to deal more effectively with the remaining lesions (now fewer in number). This is my layman's (no science / medical background) interpretation - am I right to assume this?

Most research papers I have read seem to start from the basis that ms is an auto-immune disease. The theory seems to be that it is rogue immune cells which attack the myelin which leads to nerve damage etc. Most of the drug companies seem to buy into this theory and invest in new treatments accordingly. When you look at the research projects underway, the majority appear to focus on immunology. But many posts on this site, have suggested that ms may not be an auto-immune disease -although it may be part of the disease. Who out there (i.e. in the research world) is looking at other possibilities? I assume that the myelin might start to break down for other reasons (for example, death of the cells underlying it). The immune system may be just doing what it thinks is a repair job (which scars usually are), but this is being interpreted as the cause of the disease. Has any work been done to disprove this theory?

On another issue, I have read on a number of web sites that those who experience sensory symptoms at the first attack (rather than motor symptoms) have a better chance of a milder course of ms. Why should this be so? Surely, the attacks are random and future attacks could well effect motor functions etc?


Again, apologies for all the questions but so many of you have such a wide knowledge of what's going on in relation to this disease.


Thanks

Bromley
User avatar
bromley
Family Elder
 
Posts: 1887
Joined: Fri Sep 10, 2004 3:00 pm

Advertisement

Postby OddDuck » Mon Nov 01, 2004 3:14 pm

Bromley,

I'm no expert, but here are some answers, I believe. Others here can provide additional (and probably more valuable) comments, but here comes mine (just from the top of my head).

Number one: Yes, there is intense research going on regarding the different patterns of MS. Dr. Claudia Lucchinetti (Mayo Clinic) appears to be leading the way on this aspect. She has so far found four distinct different patterns of MS. The researchers are constantly researching and trying to prove or disprove each other's hypotheses. So, yes, they are "on it", as I put it.

As far as lesion load goes. If you investigate and notice closely, for the most part, lesion load is discussed mainly in connection with RRMS, not the progressive MS types. Most of what you are referring to appears to be the discussions and theories that pertain mainly to RRMS.

SPMS and the more progressive MS types for the most part don't even involve lesion load nor inflammation, either. And some types of MS involve axonal damage, sometimes even without demyelination.

The rest of your questions, I think you will find, just goes back to the ever unresolved quandary of MS itself. The more you research (and I personally do advise that you continue to do so), I'm afraid that you may find yourself venturing more and more into the "unknown" and confusing nature of MS. That's why there is research all across the board right now. Nobody knows for certain very much about MS at all, nor can any real correlations be made between lesion load, symptoms, etc. etc.

As far as the "theory" (and it's only a theory) that experiencing sensory symptoms first "may" indicate a less severe course of the disease, I believe that comes from just statistical analysis, not from exacting medical proof. Motor control itself mainly comes from the cerebellum and the brainstem. If you are showing motor symptoms FIRST, it is likely that MS has damaged a portion of your brain (or spinal cord) that is (for lack of a better word) more "dangerous" for damage to happen in. Again, though, try to remember, that this correlation is mainly "statistical", not necessarily a medically known "fact".

As far as "future" attacks? Well, there is a certain percentage of people with RRMS who, after a speculated number of years from being diagnosed with MS, will enter into SPMS, which is a more progressive type. Again, this is a "statistical" observation.

Nobody knows why "anything" might be so. Crummy, isn't it? There are next to no answers to anything in this devious disease, is there?

Hence, why you may notice some of us being so "passionate" at times. :wink:

I hope this helps somewhat. Others here will have much better advice for you, also.

Deb

EDIT: Oh, another thing I wanted to tell you, also, is to remember that the "immune" system isn't completely what you would think of as we think of it in everyday terms. The immune system is very complex, and also includes "self-recognition" as a part of its function. Parts of the immune system fight off disease, but other parts do other things. There is the innate immune system and the adaptive (acquired) immune system. Actually, is the "immune system" involved in just about all of the MS types? Yes, in one way or another - not in "all", but in most. Sometimes so early on, that it doesn't even seem like it's the immune system at all being talked about, but it is. And is it always the same "part" of the immune system or the same place in the "timing" of what and/or when the immune system does certain things that is involved? No. And is inflammation always involved? No. You might want to do some research about the immune system and how it works. Get ready, though, for another sojourn into deep water! HAH!
User avatar
OddDuck
Contributing Author
 
Posts: 1040
Joined: Sat Jun 19, 2004 3:00 pm
Location: Tennessee

Postby BioDocFL » Mon Nov 01, 2004 6:47 pm

Bromley,
You should learn all you can about the disease, and other so-called autoimmune diseases. You will find the other diseases have many similar symptoms and the same stagnation of perception in research ideas.
Then you should become quite vocal, to organizations, doctors, us. There is an environment of apathy towards new ideas and new people in the research of these diseases. There are new ideas out there that treat MS as other than primarily an immune system malfunction. But getting those ideas heard and researched continues to be difficult unless MSers demand that these new ideas be researched and that the organizations dishing out the money are held accountable to get new researchers and ideas into the mix.
One thing you might push for at the organizations is a forum for professionals where new ideas can be discussed openly and developed into projects to test the ideas. The organizations should not continue funding the same old projects, keeping the same old researchers comfy in their mediocrity. You should also demand that the organizations allow new ideas to be presented at national meetings, instead of claiming that there isn't enough time or space for discussion. A poster or 15 minute presentation on a new theory shouldn't be a problem.
Personally, I think the right ideas are out there. They just need to get past the trolls so they can be heard.

Wesley
User avatar
BioDocFL
Family Elder
 
Posts: 251
Joined: Wed Aug 11, 2004 3:00 pm
Location: Florida

Re: Lesion load / auto-immune theory

Postby HarryZ » Mon Nov 01, 2004 6:57 pm

Bromley,

The vast majority of MS research therapies focus on what kind of lesion load on the brain you end up with. They can measure this fairly well with MRIs. But what is also known is that lesion load does not correlate with your symptoms when it comes to MS. You can have a couple of lesions and have terrible symptoms or have many lesions and few, if any, symptoms. The location of the lesions is far more important as opposed to "how many". I think what many of these researchers fail to measure is how the patient really "feels" when taking some of these potent drugs.

The auto-immune theory is really being questioned by some MS researchers and they feel that the immune system is reacting to something that has already damaged the myelin.

Of course, nobody has yet to prove any of these theories and until they can find the cause(s) of MS, finding a cure is going to be very, very difficult.

Harry
User avatar
HarryZ
Family Elder
 
Posts: 2445
Joined: Tue May 25, 2004 3:00 pm
Location: London, ON, Canada

Postby raven » Tue Nov 02, 2004 12:53 am

Lesion load is the only measurement they have. There is no way to assess neuron damage short of a post mortem. As such, even though there appears to be a poor correlation between lesion load and disability it is still the benchmark when therapies are tested.

Personally I would like to see much more data on parenchymal brain volume come out of the trials. IMHO it isn't rocket science to conclude that if the volume has decreased against controls then damage has occurred regardless of lesion activity

Robin
User avatar
raven
Family Elder
 
Posts: 240
Joined: Sat Sep 25, 2004 3:00 pm
Location: Bristol, England

Postby OddDuck » Tue Nov 02, 2004 4:42 am

For what it's worth, I TOTALLY agree with all comments posted here!!

Hang in there, Bromley. We are all "with ya". I can't tell you the frustration and "venting" about all this I've gone through from time to time.

Confusing as hell, isn't it? (Pardon my language.) And the thing is, it could be that ALL the researchers are correct! There are probably SEVERAL different sub-diseases (for lack of a better word) of MS itself!

Deb
User avatar
OddDuck
Contributing Author
 
Posts: 1040
Joined: Sat Jun 19, 2004 3:00 pm
Location: Tennessee

Postby HarryZ » Tue Nov 02, 2004 6:49 am

Robin,

Lesion load is the only measurement they have. There is no way to assess neuron damage short of a post mortem. As such, even though there appears to be a poor correlation between lesion load and disability it is still the benchmark when therapies are tested.


I agree with you that lesion load is the only measurement that is used but how do you explain to an MS patient who tries a drug, is told that his/her lesion load is reduced but their symptoms have doubled or tripled in the past year?!!

The trial researcher would likely include this patient in the very positive section of the study and say what a wonderful drug this is. There has to be a better way of doing this and having the results make more sense.

Harry
User avatar
HarryZ
Family Elder
 
Posts: 2445
Joined: Tue May 25, 2004 3:00 pm
Location: London, ON, Canada

Postby OddDuck » Tue Nov 02, 2004 8:26 am

You know, Harry, I vented about that very same thing a while ago in a letter to "somebody". I wanted to know why ELISPOT and/or MRS wasn't utilized (at the very least) in clinical trials!

I never got an answer. But does THAT surprise ya?

Deb
User avatar
OddDuck
Contributing Author
 
Posts: 1040
Joined: Sat Jun 19, 2004 3:00 pm
Location: Tennessee

Postby raven » Tue Nov 02, 2004 8:48 am

Harry

I agree with you that lesion load is the only measurement that is used but how do you explain to an MS patient who tries a drug, is told that his/her lesion load is reduced but their symptoms have doubled or tripled in the past year?!!


I can't exlain it. I wish I could, hence my interest in parenchymal brain volume. You don't see any mention of 'black holes' in trial results. I believe that some of the reasons that we don't have a cure are that we don't have effective tests to measure progression, and that we don't have a proper clinical model of the condition. EAE is only really an approximation. Encephalitis is not MS.

Robin
User avatar
raven
Family Elder
 
Posts: 240
Joined: Sat Sep 25, 2004 3:00 pm
Location: Bristol, England


Return to General Discussion

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users