This Is MS Multiple Sclerosis Knowledge & Support Community

Lyon wrote:Hi Finn,
Not trying to start an argument and admittedly my foundation is a clinical trial which is still in progress and can't really be considered "fact" but if what you mention stands any chance of being correct, what is to be made of the results found in the Tovaxin clinical trials?

Hi Bob,
you know me, there's nothing like a good argument. Besides, with only Ian and you ThisIsMS would turn into an "autoimmune consensus board" in no time ;-)

Seriously, I do believe that preventing demyelination with drugs like Tovaxin (or Campath) may be beneficial in RRMS (at least in the short term and to some extend), but is it able to halt the progression of MS for good? I personally don't think so. And according to trial results published so far, either of the drugs has been able to completely prevent symptoms from occurring. But they definitely seem to be more effective than any of the current treatments studied in double blinded clinical trials. Equally effective (in SPMS) seems to be only MBP8298.

Lyon wrote:In the entire history of MS research there is much that has been suspected but little or nothing which could be considered undeniable fact.

Yes, including autoimmunity, and the idea of inflammation being the driving force of the disease.

Lyon wrote:Considering the results they've been finding, I don't see how those results could do anything but prove that, at least in RRMS, removing the myelin reactive T cells from circulation has a profound effect on lesion formation and disability progression, at least out to the point that people have been treated so far....6 or 8 years??

So you're saying that all patients treated with Tovaxin for a longer period of time have been in complete remission during that time?

Anyway, I guess you're right, this is a wrong thread for this kind of argument. I'll try to find the extra time and energy to post more of my arguments in the Inflammation vs. neurodegeneration thread :-)

Be well.

-finn

I think all of us that have offered ourselves up to the Tovaxin trials are committed to finding answers that are indeed "outside the box". I personally find no benefit in arguing any point as to the theoretical origins of the disease when there is no therapy available to support the hypothesis. Mostly we are people who are suffering every day and unfortunately must look to the available therapies or put our faith in clinical breakthroughs.
Lars

finn wrote: So you're saying that all patients treated with Tovaxin for a longer period of time have been in complete remission during that time?

Hi finn,
Nope, I didn't say that everyone ever treated with Tovaxin is in complete remission. I've been trying to determine a date for the first clinical trial (before it was called Tovaxin) and so far I haven't been able to determine that. There are people who have been in complete remission during that whole period but I have no way of knowing how many. I do know with certainty that it hasn't been everyone.

Besides, with only Ian and you ThisIsMS would turn into an "autoimmune consensus board" in no time

Now finn, how can you say that? Ian and I go to great lengths in the attempt to convince people that we are open minded on that matter

Anyway, I guess you're right

I don't remember stating that it was the wrong thread for the argument, just that I didn't want to argue, but you don't know how long I've waited to hear you say that!! I will always treasure this moment

Bob

Finn wrote:

you know me, there's nothing like a good argument. Besides, with only Ian and you ThisIsMS would turn into an "autoimmune consensus board" in no time

I don't think I have said that MS is an auto-immune disease. If pushed I would put my money on a virus, most probably EBV. Viruses and the CNS don't go together and the JC virus which caused PML is a good example.

I do think that there is a possibility that getting in early and hard on the inflammation (caused by the immune system) seems a sensible thing to do. And I take a different view on so-called "reversible" disability - if it is reversible, then reverse it and my one Campath infusion has delivered this so far.

If MS does turn out to be primarily a neuro-degenerative disease and inflammation a response, then there's nothing I can do about it given that there are no treatments to address this. But I can do something about the inflammation and have done so. And if I get a near-normal life, as I have got, for 3,6,9 years, then I'll look back and be grateful for that, knowing I did my best with what was available at the time.

Of course SPMS and PPMS is about neuro-degeneration and I keep my fingers crossed that the researchers can come up with ways to stop the nerves from degenerating (Lamotrigine etc) and ways to promote repair (of nerve cells, axons and myelin).

Ian

robbie wrote: Bob could you just explain how mylein reactive t cells are different in people with RRMS as opposed to SPMS or PPMS. When you shift from one to the other do things change about how you are being attacked or is it just the frequency and severity that changes.

Hi robbie,
In an earlier discussion about whether or not there was reason to think that Tovaxin would work on SPMS, Tim mentioned that he thought he might have made the transition to SPMS before being treated with Tovaxin. In that same post he mentioned something about his myelin reactive T cells being a mixture of CD-4 and CD-8 which led me to believe that he was told there is some relationship between CD-4, CD-8 and being able to discern RRMS from SPMS in that way. I think I asked him to clarify but I don't think he did.

Tim did say that there were an unknown number of SPMS patients in his first study and that evidently those patients did well or the trial results wouldn't have proved so favorable.

Without having evidence to prove otherwise, my personal feeling is that there are no differences between the mrtc's and the different phases of MS but that isn't something I'd push anyone else to believe.

When you shift from one to the other do things change about how you are being attacked or is it just the frequency and severity that changes.

Believe it or not that is something that is still being researched and I read a recent study a little while ago in which the researchers questioned if there even is such a thing as PPMS and that it's likely SPMS which isn't preceded by RRMS. Because my wife has lots of lesions which haven't caused symptoms it's easy for me to believe that someone could go through the RRMS phase without knowing it and not be diagnosed until SPMS, which of course would be incorrectly be considered the mythical PPMS phase.

I'm not going to make promises that Opexa isn't willing to but my personal conviction is that if you have MS, eliminating the myelin reactive T cells will stop it.

The idea that at a certain stage disability continues in the absence of inflammation and lesions is based on MRI's which aren't discerning enough and treatments which aren't aren't effective enough because they're incorrectly directed.

Bob

Concerning remyelination I'd like to add the follwing studies:

-Prolactin shows remyelination potential in mice:
link

-In animal tests Schering showed (may/2004) that a combination therapie of schwan-cell, adenosin-monophosphat(cAMP) and the depression dug Rolipram(r) improved the walking ability of mice with spinal cord injuries by 70%.

-The Company named "Total ReCord Inc" MA USA, has a drug in pipeline (first human studies should have started in 2006) named RMx that is said to have the potential to slow scar tissue and thus allows/stimulates reconstruction of healthy brain tissue.

-In 2005 researchers (Sherman et al) found high levels of CD44 in EAE mices brains, which they clain is resposible the lack of remyelination.

(for the last three studies I only got german press-releases)

--Frank

Lars wrote:I think all of us that have offered ourselves up to the Tovaxin trials are committed to finding answers that are indeed "outside the box".

I'm sorry to say, but I think that all T-cell therapies were developed while sitting firmly inside the "MS is an inflammatory autoimmune disease" box. Few years ago it was a trend to try to develop T-cell vaccines, but only Tovaxin and NeuroVax have made it to phase II clinical trials. So obviously they seem to have potential to be better than current treatments.

Lars wrote:I personally find no benefit in arguing any point as to the theoretical origins of the disease when there is no therapy available to support the hypothesis.

I, on the other hand, find the debate on the role of inflammation and demyelination extremely interesting. You are relatively new here, but I can still remember the time when ThisIsMS was a discussion board with passionate writers supporting they own opinions and building their own theories. Comparing to that, now this is just a consensus board. Heck, I can't even remember the last time moderator was needed to calm things down here :-)

bromley wrote:I do think that there is a possibility that getting in early and hard on the inflammation (caused by the immune system) seems a sensible thing to do. And I take a different view on so-called "reversible" disability - if it is reversible, then reverse it and my one Campath infusion has delivered this so far.

If MS does turn out to be primarily a neuro-degenerative disease and inflammation a response, then there's nothing I can do about it given that there are no treatments to address this. But I can do something about the inflammation and have done so. And if I get a near-normal life, as I have got, for 3,6,9 years, then I'll look back and be grateful for that, knowing I did my best with what was available at the time.

Ian, I understand your decision and I haven't ever criticized it. I just find the "hitting inflammation early and hard" theory insufficient. On the other hand, you're dealing with the two top neuros in your country (Coles and Giovannoni), and they both seem to support the idea of early intervention with anti-inflammatories. When compared to them, my opinion should be worthless.

Lyon wrote:I will always treasure this moment

:-)

When I did my come back as a writer, my original plan was only to start one thread and keep it alive for a while. I hoped it would interest people, but the outcome really surprised me. The thread has gained over 150 answers and 7000 hits. I was also very pleased to see that great writers such as Sharon, dignan and Dom found it interesting and took part in the conversation.

Anyway, I have shared my opinion now, and I suppose it's a good time for me to concentrate on communicating in Finnish again.

Be well.

-finn

btw, where is Dom? I miss him and his posts.

finn wrote:Comparing to that, now this is just a consensus board. Heck, I can't even remember the last time moderator was needed to calm things down here

Well, I remember but that thread was removed by the administrators. ...and no, I don't see a consensus here except for that most of us are sick and tired of being sick and tired and are trying to help each other by sharing our experience and knowledge.

NHE

finn wrote:I'm sorry to say, but I think that all T-cell therapies were developed while sitting firmly inside the "MS is an inflammatory autoimmune disease" box. Few years ago it was a trend to try to develop T-cell vaccines, but only Tovaxin and NeuroVax have made it to phase II clinical trials

Dont forget Sheba medical centre with their T-Cell vaccine, who are in Phase III

Personally, I think the T-Cell vaccines will force the question, and therefore research, of why some people are not responding as well as others.

Thanks for the explination Bob, i just wonder why it seems that most of the research is done on RRMS only, that is because???

Good question Robbie. Of course I think alot of these new stem cell methods are aimed at SPMS and PPMS as well. That and some of the other nerver regeneration therapies. I sure hope those come along sooner than later.

robbie wrote:Thanks for the explination Bob, i just wonder why it seems that most of the research is done on RRMS only, that is because???

Hi robbie,
Because companies have LOTs of money invested in their treatments and they are well aware that LOTS of people (including potential investors) are watching their studies and clinical trials with great interest.

It's very important to them that their treatment perform at it's best. Some of these smaller companies, like Opexa, have everything invested that they can beg, borrow or steal. A failure, or even a percieved failure, could be the end of their company.

A company President might have good reason to be believe that their treatment would also be effective on SPMS and PPMS but RRMS is the most likely to provide good results so he/she would be considered an absolute incompetant to take the uneccessary risk of including SPMS/PPMS in a clinical trial and take the chance of tainting the perception of the RRMS results.

Opexa has to have it in mind that after the clinical trials are over and Tovaxin has the OK as an RRMS treatment they can prove, or attempt to prove that it works with the other MS phases with no risk. If it works, that's just frosting on the cake. If it doesn't work, their income from RRMS is insured.

Bob

I just want to echo Finn's closing question about Dom's whereabouts. I hope he's back to posting again soon.

Do you think Bob that with RRMS it is eaiser for companies to get better results because of the natural remission of attacks drugs or not. I would just think that if you have a drug that woks on someone with SPMS that it would take all the uncertainty out of wether the person is having a natural remission or a drug induced one. I know that placebo trials help reduce this fact but is the thought that if we eliminate RRMS that the other two will go with it.

dignan wrote:I just want to echo Finn's closing question about Dom's whereabouts. I hope he's back to posting again soon.

I PM'd him about a week ago and asked that he respond so that I could quit wondering if he's OK....he hasn't responded. I guess tonight I'll go through his old posts to see if he mentioned a vacation or something.

I did look at his old posts last night to see when his last post was. I think the last time he posted was May 16. That would be a long vacation.

robbie wrote:Do you think Bob that with RRMS it is eaiser for companies to get better results because of the natural remission of attacks, drugs or not?

Hi robbie,
I'm at lunch and only have half an hour. Those are good questions and I want to have the time to give them justice rather than just rattling something off in the time I have right now so I'll reply tonight.
Bob