Ecoclimber
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Permission to repost by Prof. G
Although this has to do with MS, the philosophy of long held medical dogama should be challenged.
ECTRIMS 2014: Daclizumab results
Daclizumab was my number 1 ECTRIMS highlight: what is it telling us about MS? #MSBlog #MSResearch
"My number one ECTRIMS highlight is the MRI daclizumab results, which shows that daclizumab reduces brain atrophy compared to Avonex in both year 1 and year
2. Why? This is telling us that daclizumab is having an effect on end-organ damage in MS and supports its positioning as a highly-effective therapy in MS. Big deal you may say?
The reason why this is so interesting is that daclizumab challenges most of the immunological dogmas about MS. Here is a drug that is not overtly immunosuppressive and has little impact on the effector function of B cells, CD4+ and CD8+ T cells. Please note these cells are meant to be key players in MS. Daclizumab also reduces T-regulatory or T-reg cell numbers and function; aren't T regs cells also meant to be a major players in MS?"
"What daclizumab does is it expands a population of cells called CD56-bright NK cells. These so called natural killer cells are part of the so called innate immune system and play a role in anti-viral responses.
Daclizumab is therefore the one DMT with a mode of action that seriously challenges the autoimmune MS dogma and possibly supports an alternative view of MS. We simply can't ignore Daclizumab's putative mode of action; it is telling us something very important about MS."
'The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.' Thomas Huxley
Arnold et al. Brain MRI results of DECIDE: a randomized, double-blind trial of DAC HYP vs. IFN β-1a in RRMS patients. ECTRIMS 2014.
Reactions:
Posted by Gavin Giovannoni at 01:57
16 comments:
Although this has to do with MS, the philosophy of long held medical dogama should be challenged.
ECTRIMS 2014: Daclizumab results
Daclizumab was my number 1 ECTRIMS highlight: what is it telling us about MS? #MSBlog #MSResearch
"My number one ECTRIMS highlight is the MRI daclizumab results, which shows that daclizumab reduces brain atrophy compared to Avonex in both year 1 and year
2. Why? This is telling us that daclizumab is having an effect on end-organ damage in MS and supports its positioning as a highly-effective therapy in MS. Big deal you may say?
The reason why this is so interesting is that daclizumab challenges most of the immunological dogmas about MS. Here is a drug that is not overtly immunosuppressive and has little impact on the effector function of B cells, CD4+ and CD8+ T cells. Please note these cells are meant to be key players in MS. Daclizumab also reduces T-regulatory or T-reg cell numbers and function; aren't T regs cells also meant to be a major players in MS?"
"What daclizumab does is it expands a population of cells called CD56-bright NK cells. These so called natural killer cells are part of the so called innate immune system and play a role in anti-viral responses.
Daclizumab is therefore the one DMT with a mode of action that seriously challenges the autoimmune MS dogma and possibly supports an alternative view of MS. We simply can't ignore Daclizumab's putative mode of action; it is telling us something very important about MS."
'The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.' Thomas Huxley
Arnold et al. Brain MRI results of DECIDE: a randomized, double-blind trial of DAC HYP vs. IFN β-1a in RRMS patients. ECTRIMS 2014.
- DAC HYP substantially reduced the burden of T2 hyperintense, Gd+, and T1 hypointense lesions (black holes) compared to IFN beta-1a.
- Improvements in MRI parameters could be seen as early as Week 24 and were sustained over 96 weeks.
- DAC HYP reduced brain atrophy compared to IFN beta-1a over 2 years of treatment.
Reactions:
Posted by Gavin Giovannoni at 01:57
16 comments:
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BouncyWednesday, September 17, 2014 11:04:00 am
Would this (after development) be considered for people with progressive MS?
Wednesday, September 17, 2014 11:58:00 am
Any evidence in support of the viral theory is welcome.
But somebody whose brother was in the daclizumab trial posted in the blog comments here (a few years ago i think). Even if that experience was a rare case, daclizumab seems scary
Wednesday, September 17, 2014 4:07:00 pm
"Daclizumab also reduces T-regulatory or T-reg cell numbers and function; aren't T regs cells also meant to be a major players in MS?"
Since this drug is a monoclonal antibody to CD25, it seems to be a method of killing off Tregs so that a new population can be regenerated. Since there is a mountain of evidence that Tregs are defective in MS as well as other autoimmune diseases, it makes sense to me. Remember rebooting the immune system?
But I find your line of logic very entertaining. Keep it comming!
MouseDoctor2Wednesday, September 17, 2014 4:23:00 pm
But all the immunological dogma would suggest that killing off CD25 positive T reg cells should trigger relapses and make MS worse. It doesn't, it stops relapses, suggesting there's something wrong with the theory. We've raised this question with several eminent T-Regers and they um and ah, shuffle nervously for a while, then shout "Oooh look a squirrel" and make a hasty exit.
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AnonymousWednesday, September 17, 2014 4:40:00 pm
So your saying that killing off Tregs will immediately cause a relapse? With this logic, an msers should always be experincing a relapse since Tregs have been shown to be deficient.
I can imagine why other scientists in the field look at you with a puzzled expression.
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MouseDoctorWednesday, September 17, 2014 5:03:00 pm
Was it a squirrel or a lemming
Sorry folks I couldn't resist it...please see me suitably repromanded
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AnonymousWednesday, September 17, 2014 5:08:00 pm
I guess the rest of the lemmings have discovered that Daclizumab may not even effect Tregs.
http://www.ncbi.nlm.nih.gov/pubmed/17109733
Interesting how science works outside of a locked mouse cage.
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MouseDoctor2Wednesday, September 17, 2014 5:11:00 pm
If T regs really are deficient in MS, then getting rid of those that are left should make things worse. Depleting CD25 T reg cells by anti CD25 monoclonal antibodies increases disease severity in mouse models of multiple sclerosis so a reasonable assumption is that you would expect the same in MS. You don't, which is puzzling.
Capiche?
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MouseDoctor2Wednesday, September 17, 2014 5:38:00 pm
Anon 5:08
I see you reference and counter it with this one.
http://www.ncbi.nlm.nih.gov/pubmed/19364932
Interesting how dogma can cloud the mind.
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AnonymousWednesday, September 17, 2014 7:39:00 pm
I see your dogma and raise you a lemming:
http://www.ncbi.nlm.nih.gov/m/pubmed/19141125/?i=3&from=/17109733/related
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MouseDoctorWednesday, September 17, 2014 11:34:00 pm
afraid its not poker......
will have look at your posts
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MouseDoctor2Thursday, September 18, 2014 11:14:00 am
Anon 7.39
Read your ref This study used a different anti-CD25 short-term which only seems to block the CD25 receptor for a short time and doesn't cause the death of the T cells. It's therefore not really comparable to daclizumab.
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AnonymousThursday, September 18, 2014 7:23:00 pm
To say that an anti-CD25 therapy doesn't cause a relapse is proof that Tregs are not the cause of autoimmunity is a statement comming from some pretty sheltered people.
I guess if your work is based on trying to disporove other peoples work instead of making new discoveries, this is expected.
The fact is the Tregs are not fully understood, which there are people currently working on this:
http://www.ncbi.nlm.nih.gov/pubmed/21856944
But if you cant replicate others work, no use for further research or thought. Instead, it must be caused by a virus.
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MouseDoctor2Friday, September 19, 2014 11:15:00 am
Please explain the results with reference to the T reg hypothesis rather than the same old tired ad hominem. We want to cure MS, we don't care what mechanism achieves that goal.
As for your comment about trying to disprove other peoples work, I suggest you read some Karl Popper regarding testing a hypothesis. The Daclimuzumab data already shows the T reg theory has some holes in it with regard to MS.
Vasilis VasilopoulosThursday, September 18, 2014 8:36:00 pm
A drop from 0.74 to 0.67 (0.07) and 0.56 to 0.52 (0.04) compared to the awesome interferon? I don't believe it! This is a miracle cure or what...?
MouseDoctor2Friday, September 19, 2014 11:09:00 am
Long time no hear VV and still brimming with positivivity! It's a start.
Welcome back.
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