Progression

[HarryZ]

Brock,

Of all of the people who post frequently on thisisms.com, does anyone actually have any sort of biological research background? I am aware of Dr. Wheldon, but are there any others? Does anyone have access to resources that have the ability to dig in to this disease with out bias, Professors? A long shot question, but had to ask.

Brock

My cousin's son is a PhD researcher in medical chemical toxicity. Unfortunately he has not done any work in the MS field and I have only briefly ever spoken to him about MS and what is going on in that area. A nice contact but not in the right area

[sojourner]

Brock,

You have expressed the feelings of a lot of people (and family members) with chronic illnesses! There is tons of research going on, but that never translates into effective treatment.

If one is looking for a place where there are very knowledgable "experts" and laymen--go to CPn Help.org. You will be astounded by the amount of information and ongoing deliberation, support and search for knowledge there.

The facts are clear---most Drs. in their suites of offices in their professional buildings are not going to venture outside of the box that they practice medicine in. ( This is not meant to offend those in the medical profession!) They simply are administrators of the goods that they are offered by the drug companies. Reserachers are also stuck in their little niches often unable to connect the dots

My husband has decided to leave no stone unturned in fighting this illness. We weighed the risks and possible benefits of an empirical course of abx per the Wheldon protocol and have decided to start treatment. He is also following the adjunct supplements and is continuing weekly Avonex.
At the onset of his illness, we were good little soldiers believing the neuro knew everything. Do we know better? I don't know, but I do know we have a real and vested interest in my husband's health and his neuro does not!

I am sorry for the length of this, however, just one more thing. This summer I languished in my daughter's physician's office knowing she had Kawasaki syndrome (a rare fever illness in children-which is the number one cause of acquired heart problems in kids). My doctor refused the notion--dismissed me on two seperate visits. He did not order blood work that would have shown alarming sed rate and c-reactive protein results. This disease is only treatable during the first 10 days. If it is treated children face a much lesser chance of developing anuerisms and other artery problems.

I, even though in my gut I knew she had Kawasaki, demanded nothing. I threw out my own feelings and let him lead us down the wrong path. On day 10 her fever subsided and her hands began to peel from the nails down---I knew that that meant it was indeed Kawasaki, took her immediately to the dr. and he finally ordered the proper blood tests and sent us directly to the hospital. We missed the window of treatment, the infectious disease people did diagnose her with Kawasaki and we have been very lucky so far---but she now needs to see a cardiologist every six months for a long time---scary

Ultimately, we are responsible for ourselves. I will never again allow an unknowing dr. pretend to know everything. MS is a mystery and they should admit that.

Again, I apologize for the length, Lexy

[viper498]

Sarah,

Good point. Nashville isn't really that far from me. I will definitely check out CPn Help.com.

This is the only MS site i've posted to forums on. I can tell you that everyone here seems to be very informed. Its comforting to know that there are other people out there that feel the same way, and see the same things you see. I am going to immerse myself in ABX research now. I may consider this.

The only symptom of MS I've had so far is Nystagmus presenting in my Right eye in June of 2005. The hospital put me through an MRI, and found a lot of small spots on my Brain, however none on my spine. They performed a spinal tap, results came back high for CSF protein, the max threshold was 40, my score was 42.6, and high for glucose max was 70, my score was 75 (any idea what that means?). I had a VEP test, my left eye was slower than it should have been (strangely enough, considering my right eye was the affected eye).

I've not had any other symptoms. I take Rebif, and follow, in great part the BBB, watching what I eat, and taking many supplements.

I wonder if people who have the CPN infection follow a vague, but similar pattern of onset, and progression???? I was 25 years old when I had the CIS. Sorry for so many questions, and such long posts.


Lexi, I totally agree. Everyone has to be their own medical advocate. Doctors, or at least most of them, look at you like a number, and since they try to see so many patients, there is no way they could really care about the outcome of everyones specific situation. As long as your Ins. payment clears, they are happy. I've felt this way even before I was diagnosed with MS. Doctors have lost site of what is important, the patient. Its money now.

[Shayk]

Welcome to ThisIsMS also Viper.

All--I know it seems like an interruption to the discussion and I apologize for that but I wanted to respond to Jaded’s earlier inquiry.

Jaded—I don’t think there’s any easy way to tie all of this together. Researchers interested in HPA hyperactivity (hypersecretion of cortisol I think) and MS have started to try and tie some things together from that tiny corner of MS world of research. So, with regard to the stress hormone “cortisol” and/or glucocorticoids, here are a couple of abstracts about that.

The Role of Stress Response Systems for the Pathogenesis and Progression of MS

Insensitivity to glucocorticoid and beta-adrenergic modulation might be involved in overshooting inflammation in MS, whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability.

As nearly as I’ve been able to understand (since I understand very little in fact is why I feel compelled to provide links to abstracts many times) is that HPA hyperactivity translates to hypersecretion of the stress hormone cortisol.

HPA Axis Activity Predicts Disease Progression in MS

In this longitudinal study over a 3-year follow-up period, we report that patients who exhibited stronger HPA reactivity at baseline were significantly more likely to experience progression as measured by the Expanded Disability Status Scale (EDSS) during the follow-up period. Furthermore, HPA axis activity correlated with progression ratings and cognitive impairment three years later. Tests of HPA axis activity may be useful biomarkers for disease progression in MS.

IMO persistently high cortisol levels as a result of the hypersecretion may be bad for MS. Glutamate toxicity and intracellular Ca2+ concentrations have recently gotten some attention in MS research. Here’s an abstract I’ve posted a couple of times I think.
Estrogens Attenuate and Corticosterone (Cortisol) Exacerbates Excitotoxicity, Oxidative Injury and Amyloid Beta-Peptide Toxicity in Hippocampal Neurons (in rats)

Steroid hormones, particularly estrogens and glucocorticoids, may play roles in the pathogenesis of neurodegenerative disorders, but their mechanisms of action are not known. We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid beta-peptide (A beta) toxicity….

In contrast, corticosterone exacerbated neuronal injury induced by glutamate, FeSO4, and A beta.

Estrogens and progesterone also attenuated A beta- and glutamate-induced elevation of intracellular free Ca2+ concentrations.

I think corticosterone is the stress hormone cortisol. Although this is not MS research, this abstract, The Possibility of Neurotoxicity in the Hippocampus in Major Depression: A Primer on Neuron Death reinforces a connection between hypersecretion of cortisol, glutamate excitotoxicity and Ca2+ concentrations in the loss of neurons, specifically in the hippocampus.

article reviews current knowledge about how hippocampal neurons die during insults, focusing on issues related to the trafficking of glutamate and calcium, glutamate receptor subtypes, oxygen radical generation, programmed cell death, and neuronal defenses.

glucocorticoids, the adrenal steroids secreted during stress, may play a contributing role to any such neuron loss. The subtypes of depression associated with the hippocampal atrophy typically involve significant hypersecretion of glucocorticoids, and the steroid has a variety of adverse effects in the hippocampus, including causing overt neuron loss.

So, I definitely tie the hypersecretion of cortisol (HPA hyperactivity) to neuronal loss. People with MS seem to lose neurons (i.e., brain atrophy) and the HPA hyperactivity has been linked with disease progression in people with MS (per the first abstract). And, while this later abstract is on depression per se and not depression in people with MS, it is generally well known (I think) that many people with MS may also suffer from depression, that may or may not be “co-existing” with MS.

Jaded I hope this helps a tiny bit. It’s a bit about why I’m personally intrigued by the case I posted about chromosome 6 and the hypersecretion of corticotrophins. It seems to me (no scientific or medical background) that hypersecretion of cortisol can cause gluatamate excitotoxicity and neuronal loss. I seriously question if it may be operational in the MS disease process as well. That is a personal opinion only. My cortisol levels were definitely high when I had my hormones tested and I had NO progesterone.

Jaded--as for steroids and MS, I’m happy to learn they’re being studied for MS. Some time ago I posted info that methlyprednisolone dose dependently contributed to axonal loss in rats and interfered with a neuroprotective pathway. Personally, I’m very skeptical of them. They are no longer recommended for use in traumatic brain injuries where inflammation is a major concern.

As to LDN, it’s my understanding that the hypothesis about its mode of action pertains to glutamate excitotoxicity as well.

Brock—I have no biological background and don’t know anyone to lean on either with or without a bias. I agree with Sojourner, we need to do a lot ourselves. If you’re interested in a more scientific take on MS, I’d also recommend the Accelerated Cure Project . That link is to the news update.

Take care everyone. I do believe there’s progress and that they’re starting to focus in on neurodegeneration and not just inflammation. Another long post I know but I'll back off.

Sharon

[viper498]

Shayk, Everyone else,

Sorry to take the Topic off course. I got off on a tangent.

Regards,
Brock

[Shayk]

Brock

You didn't take it off topic. No need to apologize IMO. Welcome again. I like discussion.

Sharon

[Jaded]

Sharon

Thanks for your reply. It's interesting stuff.

I am pleased that there is now research looking at pulling some theories together. That might get us somewhere.

I think we need an MS awareness campaign/group. We need to highlight the scam that is being run by the current pharmaceuticals, and the neuros pushing people down the steroids route. There has to be something behind the fact that there have been no cures found in the past couple of decades, and, as Ian rightly says, we can see our car using a satellite system on Google Earth.....how does that work for revolutionary science?

By the way, when I had my lumbar puncture, the doctor who attended to me, who knows more about MS than my neuro, said that even the crabs drugs were untested in the long-term. So we are all guinea pigs then.

We all deserve better than this.

J.

[bromley]

Dear All,

Thanks to all those who contributed to this thread. I thought it was worth highlighting the work on progression as it's pretty clear that this disease is more than about a little bit of inflammation in the brain which steroids and the CRAB drugs can deal with. EAE can be cured, but it's not MS. The researchers need to answer the following question before progress will be seen:

Is MS an inflammatory disease of the CNS which causes degeneration of nerve fibres (axons / neurones) or is MS a degenerative disease of nerve fibres which (in some cases e.g. RR) also leads to inflammation / immune system involvement?


Many MS 'experts' appear to have opted for the former and their approach has been to prescibe steroids and CRAB drugs as a consequence. But I have yet to see evidence that this approach has stopped progression of the disease (or slowed it down that much).

But the tide appears to be on the turn with a little bit more focus on the reasons why the nerve fibres degenerate (although still with an eye for degeneration resulting from the inflammation / immune system).

Stopping progression must be the goal now (and maybe repairing the damage once progression has been stopped). I want my obituary to read Ian XXXXXXX, died at home age 84, surrounded by his children and grandchildren, not Ian XXXXXXX, died age 51, after a long battle with MS.

The MSIF states that 'the new century will see our victory'. I can't wait another 94 years. The end of the decade should be tha target, giving plenty of time for the CRAB maufacturers to come up with some expensive drugs for some other disease.

Ian

[SarahLonglands]

Brock,

So as not to take this off on another tangent, I'll send you a reply by email!

Sarah

[gwa]

bromley posted,

"Many MS 'experts' appear to have opted for the former and their approach has been to prescibe steroids and CRAB drugs as a consequence. But I have yet to see evidence that this approach has stopped progression of the disease (or slowed it down that much). "

I also question the research that backs up these drugs. Many of the people that are on these drugs are in much worse shape than I am in, and I have had this disease for almost 35 years.

The first decade was the roughest and I had a relapse every 4 months the first two years. Then the disease calmed down and I had only a relapse once or twice a year for the next decade.

The past two decades have been a very slow decline and no major relapses as I am now SPMS.

My own track with MS seems to correlate with the people who now take one of the CRABS. So I wonder if the meds are really slowing down their disease or if they would be in their current situation without the meds.

I know that I am waiting for something that really works and stops the disease or repairs me.

gwa

[HarryZ]

GWA,

I also question the research that backs up these drugs. Many of the people that are on these drugs are in much worse shape than I am in, and I have had this disease for almost 35 years.

Ever read the multitude of trial data on the CRABs....they pretty much all state that there has been a reduction in certain percentage of lesions on MRIs and a reduction in the number of exacerbations compared to the placebo patients. Well, we know that lesions come and go and there is little correlation between T1 weighted MRIs and symptoms and disease progression. And while it is nice to have fewer exacerbations, the natural progression of the disease doesn't appear to be affected.

So we have all these MS patients on the CRABs, paying out approx $15000- 18000 a year, many suffering from some nasty side effects (which never seem to get mentioned when these drugs are advertised) yet in the long run, we see very little if any effect on their MS. And we know that some patients can become much worse on them!

My wife has had MS for 35 years as well and back then there wasn't any such thing as a CRAB. And she went 20 years without any problems while living a very active, sport-filled life....and she took nothing for her MS.

Kind of makes you sit down and think just who is benefiting the most from these potent drugs....mose likely the bank accounts of the companies that make them because the patients don't appear to be any better off while using them.

Harry

[gwa]

Harry,

My sentiments exactly with everything that you have said.

gwa

[bromley]

Harry / GWA,


There must be historical data of MS patients who have not taken any of the CRAB drugs. My parents (in an attempt to cheer me up) often say 'Mrs Smith down the road has had it for 25 years and is doing ok etc etc'. And these are individuals who have never been near one of the CRABs.

But the way these drugs are marketed suggests that if you don't get on them quickly you'll be going rapidly downhill, much quicker than would be the case if you did not.

I hate the way that the marketing always shows young people in bike races, climbing mountains etc. But there's never a picture of someone in a wheelchair with the caption - sorry this drug won't do anything for you!.

In the UK there is a TV advert for a wood varnish and the slogan is 'it does exactly what it says on the tin'. But what exactly do the CRABs say on the tin? There's certainly no money back guarantee if they don't work. It's funny how they all reduce exacerbations by the same amount - 30%. But as you say Harry what does this really mean?

Ian

[gibbledygook]

Some doctors reckon the 30% reduction in exacerbations is placebo effect anyway so the drugs could be completely ineffectual!!

[HarryZ]

Ian,

There must be historical data of MS patients who have not taken any of the CRAB drugs.

In all of the years that I have been following MS research, I have not seen any kind of formal study published that states how patients have faired without taking any kind of medication for their MS. We know how the placebo patients have done in the formal clinical trials but that would represent but a small percentage of those who took nothing.

But the way these drugs are marketed suggests that if you don't get on them quickly you'll be going rapidly downhill, much quicker than would be the case if you did not.

They do exactly that and have convinced many docs to follow exactly that protocol. Don't know if you have ever read the report by the John Hopkins MS people who suggest that MS patients wait to see how their MS may progress before going on any of the CRABs. That article about 1 1/2 years ago really caused a bit of a flap in the MS medical community and I'm sure with the CRAB makers as well.

It's funny how they all reduce exacerbations by the same amount - 30%. But as you say Harry what does this really mean?

Can you imagine a drug company advertising an antibiotic and stating that it will help about 1/3 of the people who take it and only reduce the infection by about 1/3 as well??!! And we will charge you $ 1500 for a month's supply of it!!!

I have to admit that the CRAB drug makers have done a masterful job at convincing many people in the MS world that these drugs are what you must take if there is any chance at becoming better. And keeping the price at those levels for the past 13 years!!! Perhaps I should have worked for a pharma all these years!

Harry