Combo treatment

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Postby Lyon » Sat Jul 22, 2006 1:33 pm

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Postby bromley » Sun Jul 23, 2006 3:03 am

Bob,

On Tovaxin - the drug has moved on to the next trial phase - I think Phase II. Early results suggest a 90% reduction in relapses and improvements in EDSS.

There are other T cell vaccination treatments in the pipeline. The theory looks good - if MS is purely a T cell mediated disease. Rituxan targets B cells which may suggest that some cases are B cell mediated.

Campath targets both T cells and B cells.

Bone Marrow Transplantation wipes out the whole immune system.

I forgot to mention Daclizumab which in a small trial showed stabilisation or improvements in EDSS. Over the last year or so there has been a focus on T-Reg cells which are increased by Daclizumab.

Hopefully some of these trials will throw some further light on what drives this disease on and how it might be halted.

Ian
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Postby HarryZ » Sun Jul 23, 2006 7:21 am

Hi Bob,

I think that the severity and possible permanent effects of an exacerbation depend on just what part of the brain the lesion appears. We know that the number of lesions are not nearly as important as the location.

The drug company clinical trials focus a lot in the reduction of the number of lesions. But lesions come and go and they don't correlate with disease symptoms. Just a couple of lesions in the wrong part of the brain can cause some severe damage to the MS patient.

In the case of my uncle, his MS stabilized to a large degree when he was in his 50's. He was always able to walk on his own (albeit not any long distance). He suffered a lot from bladder problems over the years and the ever present fatigue. Hot and humid weather did him in all the time.
In his 60's, he came down with hairy cell leukemia and after a couple of years died from that.

Now had CRAB drugs been available to him back then and he used them, the docs would have stated that they allowed him to live a normal as possible life under the circumstances. But that's all he ever took were the vitamin B12 shots because that's all they had back then. He was a classical example of the MS doing what it wanted to do and when it wanted to do it. Others were not as fortunate while others had it better. Kind of makes you wonder if the medical world has really progressed all that much when it comes to treating this disease.

Harry
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Postby Lyon » Sun Jul 23, 2006 7:56 am

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Postby HarryZ » Sun Jul 23, 2006 11:14 am

Bob,

Not that MS sufferers need any more dark clouds in their horizon but I've always wondered why higher cancer risks have never been associated with MS and other destructive autoimmune diseases.


I can't recall reading over the years about MS patients having higher cancer rates or some of the auto-immune diseases over the normal population. I can only assume that they don't.

I'm still not convinced that MS is an auto-immune disease in origin and that the immune system in MS patients reacts to the inflammation that is caused when the myelin is attacked by some other mechanism. If it was simply auto-immune then the CRAB drugs, in my opinion, would have a much greater effect on the progression of the disease.

Harry
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Postby Lyon » Sun Jul 23, 2006 6:15 pm

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Postby HarryZ » Sun Jul 23, 2006 8:43 pm

Bob,

I'm a firm believer that MS is autoimmune but I also believe, and I think it's widely believed that MS originates with a trigger and it seems to me that trigger would have to be either environmental (carbon monoxide, etc..) or an event (trauma, etc) along with genetic suceptibility.


In 1935, the scientist Thomas Rivers injected a foreign protein (antigen) into the myelin of the spinal cord of a dog and the dog developed hind leg weakness and symptoms similar to MS. And thus began the theory that MS was an auto-immune disease....a theory which 70 years later has still not been proven!!!

About 1 1/2 years ago, Drs. Prineas and Barrett perform an autopsy (within 18 hours of death)on a young 17 year lady who dies from a severe MS exacerbation and they don't find any evidence of the immune system being involved in the lesion that caused her respiratory system to shut down.

Since they were developed in the early 90's, the CRAB's have had only minimal effect on MS patients and they try to do this by "playing" with the person's immune system.

As much as I would like to, I simply cannot subscribe to the auto-immune theory for MS. I think there is something else going on that triggers the damage to the myelin and the immune system is reacting to this trigger and subsequent inflammation when demyelination takes place.

And as long as the research continues to be fixated with the auto-immune theory, I believe that we are going to continue to end up with the results we have achieved in the previous 70 years of research....and as Dr. Behan states in his Pathogenesis of MS paper, that has been abysmal!

Of course this is only my opinion and most will disagree with it.

Take care.

Harry
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Re: Combo treatment

Postby NHE » Mon Jul 24, 2006 3:25 am

Here's some more food for thought regarding the subject of autoimmunity.

    The enemy within: keeping self-reactive T cells at bay in the periphery
    L.S. Walker and A.K. Abbas, 2002, Nat Rev Immunol, 2(1): 11-19.

    The remarkable capacity of the mammalian immune system to coordinate deadly attacks against numerous invading pathogens, yet turn a blind eye to self-tissues continues to fascinate immunologists. It has been clear for some time that immune cells capable of recognizing self-proteins exist in normal individuals without seemingly causing harm. The 'peripheral tolerance' mechanisms that keep these cells in check are the focus of intense research, not least because defects in these pathways might cause autoimmune diseases. In this review, new developments in our understanding of peripheral tolerance are discussed.

NHE
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Postby bromley » Mon Jul 24, 2006 4:20 am

Here is the UK MS Society coverage of the combo treatment and details of the trial (UK only)

http://www.mssociety.org.uk/go.rm?id=17206

This story has received lots of coverage in the UK with the annoying consequence that friends and family members have alerted me to the 'miracle' treatment, or sent me the press cuttings. They mean well, but tend to read these sorts of stories at face value. Hopefully, it will show as much promise in the trial and become another option.

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Postby HarryZ » Mon Jul 24, 2006 6:10 am

Ian,

This story has received lots of coverage in the UK with the annoying consequence that friends and family members have alerted me to the 'miracle' treatment, or sent me the press cuttings. They mean well, but tend to read these sorts of stories at face value. Hopefully, it will show as much promise in the trial and become another option.


Oh don't Marg and I only know too well the same reaction from friends and relatives over the years when similar articles appeared in the press!

I'm thinking that it will take about 6 months for the people in the UK to set up this next-step trial which will likely last for 2 years if they classify it as Phase III. Then again, because both these drugs have been around for a while, perhaps they may be able to get accepted answers within 1 year.

Harry
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Postby bromley » Mon Jul 24, 2006 7:18 am

Harry,

The worse was the coverage in the UK of the stem cell injections in Holland. My dad keeps saying to me "I'll give you the £14,000!".

30 seconds ago a colleague just said "did you see the press at the weekend about a new treatment?". If I strangle the next person who says this I might need you as a witness for the defence.

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Postby HarryZ » Mon Jul 24, 2006 9:12 am

Ian,

The worse was the coverage in the UK of the stem cell injections in Holland. My dad keeps saying to me "I'll give you the £14,000!".


That's a lot of money for a treatment that has very little known about it and its effect on MS!! Stem cell treatment is becoming a big time business in some countries and I'm concerned that it is attracting people who are desperate....whether it's with MS or other disease.

30 seconds ago a colleague just said "did you see the press at the weekend about a new treatment?". If I strangle the next person who says this I might need you as a witness for the defence.


I'd be glad to testify on your behalf but I'm sure the prosecutor may check my postings on the net and then try and make my testimony an issue of credibility :D

Harry
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Postby amelia » Mon Jul 24, 2006 11:06 am

AHHHHH! Well meaning family members and cures or fixes for MS. Gary's Dad keeps buying him all sorts of glasses to fix his blindness. Can't seem to make him understand that the blindness is not fixable with glasses. :roll:
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Postby Lyon » Mon Jul 24, 2006 2:48 pm

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Postby sh8un » Mon Jul 24, 2006 3:18 pm

Hi Lyon
Nice to see a pic of you. There are some theories out there about the so called "triggers" of MS and other demyleinating diseases. These triggers ( be it a virus, bacteria or whatever) cause the body to have an immune reaction where antibodies are made for that particular antigen. These antigens are thought to resemble mylein. That is why the antibodies that are made accidentally starts to attack the body itself. In this sense there is an autoimmune response where the body mistakes self for foreign. Kind of like Guillian-Barre. I may not really be sure where you are confused so I hope that this helps. I think that you are saying the same thing but I am not sure.
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