This Is MS Multiple Sclerosis Community: Knowledge & Support

Thanks for the link Ian.

I don't want to be a downer but after the mapping of the human genome things aren't going as quickly as I had hoped.

It sounds like there is still a long process ahead and I kind of thought success would involve "tweaking" the genes to make MS go away without drugs. I'm a little dissapointed that the article still talked about developing drugs to do it.

Bob

Good article, bromley. This is the first time I have seen definite genes tied to MS. It looks like the scientists have found a good starting point for drugs.

They indicate some drugs may already be on the market.

gwa

gwa wrote:

Obviously I don't have any idea what they're referencing, but there's been some research on estrogen, the TCR Peptide Vaccine (?Neurovax I think) and the FOXP3 gene the article mentions.

Decreased FOXP3 Levels in MS Patients

Congruent Effects of Estrogen and T-cell Receptor Peptide Therapy on Regulatory T cells in EAE and MS.


Despite the finding of low FOXP3 levels in people with RRMS, it's not clear that people with SPMS have that issue, per this abstract:

Secondary Progressive in Contrast to RRMS Patients Show a Normal CD4+CD25+ regulatory T-cell function and FOXP3 Expression.

That makes me wonder how important this FOXP3 stuff is. They are making progress though and that's the good news.

Sharon

Research demonstrating misregulation of specific genes in MS has been around for a little while. For example, this paper from 2003 discusses the misregulation of apoptosis genes in T-cells during active MS.

Expression ratios of the Bcl-2 family proteins and disease activity in multiple sclerosis.
J Neuroimmunol. 2003 Jan;134(1-2):158-65.

There is emerging evidence that failure of apoptosis (programmed cell death) of potentially pathogenic T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). The commitment of T lymphocytes to die is partly regulated by the Bcl-2 family proteins, which act as a checkpoint upstream of mitochondrial dysfunction. These proteins include the death antagonists Bcl-2 and Bcl-X(L), and death agonists Bax and Bad. Recent studies suggest that altered expression of Bcl-2 family proteins in T lymphocytes is involved in promoting cellular resistance to apoptosis in patients with MS. However, the relationship between these alterations in Bcl-2 proteins expression and clinical disease activity has not yet been evaluated. In this study, we analyzed the expression ratios of pro- to anti-apoptosis Bcl-2 family proteins in patients with clinically active MS and compared results to corresponding ratios in patients with stable MS and relevant control groups. We observed a significant reduction in the expression ratios of pro- to anti-apoptosis Bcl-2 members in peripheral lymphocytes from patients with active MS when compared to corresponding ratios in patients with stable MS or other controls. This imbalance in the expression ratios of pro- and anti-apoptosis proteins was functionally active in reducing cellular susceptibility to apoptosis in active MS. It also correlated with clinical features of disease activity, such as the number of gadolinium-enhancing MRI lesions and clinical relapses. Our findings indicate that dysregulated expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of clinically active multiple sclerosis.

...and here's another from 1998 that also discusses Bcl-2.

Bcl-2 expressing T lymphocytes in multiple sclerosis lesions.
Neuropathol Appl Neurobiol. 1998 Jun;24(3):202-8.

Multiple sclerosis (MS) is a chromatic inflammatory disease of the central nervous system. T lymphocytes play a major role in the pathogenesis of the disease. The exact mechanisms by which the inflammation is regulated in MS have not yet been defined. Studies in animal models of MS suggest that apoptosis of T cells is the main factor terminating inflammation. The process of apoptosis itself is regulated by a range of pro- and anti-apoptotic proteins. The bcl-2 gene family is an important member of these proteins. The present study investigated the expression of the anti-apoptotic protein bcl-2 in 11 chronic MS cases including five relapsing-remitting and six chronic progressive MS patients. A total of 35 lesions containing all stages of demyelinating activity were studied. The number of CD 3-positive T cells and the absolute and relative numbers of T cells expressing bcl-2 were determined by double immunocytochemistry. Bcl-2 is expressed by T lymphocytes in MS plaques. Patients with chronic progressive MS have a higher proportion of bcl-2 expressing T cells than patients with relapsing remitting disease. Highest numbers of bcl-2-positive T lymphocytes were found in remyelinating and demyelinated lesions, whereas active demyelinating lesions revealed lower numbers. These data indicate that cell-death-related proteins such as the anti-apoptotic protein bcl-2 are expressed in MS lesions and that they might have important effects on the regulation of elimination or persistence of inflammatory cells in the central nervous system.

NHE

It still doesn't seem logical to me that they can treat MS until they know what the cause is. Just because they find genes that make someone more likely to have MS doesn't mean you can some how eliminate that gene and cure the condition (or at least I wouldn't think). Its imperative that they discover the cause or causes of MS before revolutionary treaments are available (I hope I am wrong, but I fear not).

Brock

I REALLY dont know what I am talking about, however, if I do happen to understand this correctly, I think the idea is once you know which genes are involved, you can then create a substance/chemical which could disable or down regulate the effect of those specific genes.

Hi Brock,
It sounds like your definition of "cure" is similar to mine. "Find the cause/s and reverse or neutralize those causes". Therein (hopefully) lies the "cure".

Despite the fact that we still don't know the cause/s I'm still pretty hopeful for some of the things in trial which seem to serve to "reboot" the immune system like Campath1h and HDC and also Tovaxin which hopefully serves to selectively eliminate ALL OF and JUST the offending T cells. Things look good so far but, of course, it ain't over until the heavyset woman sings.
Bob

Bob, you are such a diplomat I too am hopeful about some of the treatments in trials. It's obvious that completely supressing the immune system is not the answer. I think any progress in understanding MS and the genes that identify it is helpful. And if by indentifying these genes they are able to develop more effective drugs, I'm all for that too. If they could develop a drug that would control MS without actually curing it, I'd be happy to take it for the rest of my life. I know that the ultimate goal is a cure but I know that that could be a long way off and the prospect of my disease progressing scares the crap out of me. I would like to see exactly where research on myelin repair and neuro protection is at. You see vague timelines and mice trials but I've never actually seen any concrete research progress. Is 2010 when they expect to be ready to start testing in humans or is that when they expect there to actually be a treatment on the market? Does anyone know? Just curious. I've not been feeling very well lately and that always makes me anxious to hear some good news.

Hi Cure,
I don't know the answer to that one. Did you actually read 2010 somewhere because in a way regarding suspected neuroprotection they are already trialing that (lamotrigine) but as far as myelin repair....I didn't think they were at a point in which they could realistically project a date? Don't know, hopefully someone else knows more about that one. My wife is feeling well but the Tovaxin coordinator called her yesterday and said she had another new lesion on her recent MRI. While it's wonderful that she isn't experiencing anything bad from these lesions it's scaring the crap out of us that she keeps getting more of them. Dosing with Tovaxin hasn't yet begun and at this rate a possible year on placebo is getting scarier and scarier. Not to push the helminth parasites yet again but that is exactly what is most hopeful about them. They don't just suppress the immune system, they modulate it...controlling multiple aspects of the immune system as needed. Sorry, more shameless plugging of the helminths on my part
Bob

Bob, I'll forgive you this time for calling me the wrong name but don't let it happen again!! I was speaking of the timelines that Promise 2010 and the Myelin Repair project have used. The Myelin Repair project actually mentions their hopes of licensing a product by 2009 so that's where my question came from. As I've mentioned before, I'm ready to swallow a worm if it becomes available and will help control my MS. It's easy to see how someone can become desperate when this disease is getting the best of them. That's why I couldn't possibly face another day if I didn't have hope that these days would end.

Sorry Scooby, I feel so dumb! We rented a movie (Crank) and the family was yelling for me to get into the other room to watch it and I was in a hurry. If I remember correctly, you and Cure have the same or similar avatar and I evidently glossed over the name when I responded. I'm a firm believer that the past is the clearest portal to the future. Some people don't look far enough into the past and have convinced themselves that because MS has never been cured in the past, it never will be. With a broader viewpoint of the past it's obvious that everything we set out to accomplish is eventually and invariably met with success. Sure a long, dark period always preceeds success but I'm convinced that we are at the tail end of the dark corridor...regarding stopping the disease process.

Regarding myelin regeneration?? Jamie hasn't got noticeable disability so I haven't spent much time on that. I keep telling myself to check out the myelin repair project and haven't gotten around to it yet but I will tomorrow. Something very hopeful to aid the body in myelin repair available or at least in trial by 2010 would be very nice!
Bob

PS...I just checked. Cure has no avatar. My brain is mush.

I was tempted to go and set my avtar to be the same as scoobyjude just to confuse you. Or even better, another one, so that both statements would be wrong!

Curently I am hosting jimmylegs avtar in my photobucket. One day I'm gunna replace it with something she wont be to happy about; but lets just keep that between ourselves. She never actually reads these forums. just like you...

Hi Cure,
Now that wouldn't be nice, considering that I'm clinging dearly to the little remaining sanity that I have Guilty as charged! I read and think it's sinking in but by the time I get to play on the computer I'm so tired that my brain can't process the things that I read. Kind of a waste!
Bob

There must be something in the water here. I also live in a (Western) suburb of Chicago and have found myself spouting these same ideas:

a) Just supressing the immune system is a nice beginning but more metabolic pathways may need to be addressed.

b) If I had to take a pill everyday to arrest my MS and regenerate damaged cells then I would gladly do this.

and most importantly

c) I don't want a cure. A cure might cost $600 trillion and take 30 years. But a pill might only cost $3 billion and take only four years.

I would be more than willing to be a paying patient for life...Oh, scratch that...I already am.