2019 Review: MS in 2018: new therapies and biomarkers

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jimmylegs
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2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Sat Jan 12, 2019 2:16 pm

Multiple sclerosis in 2018: new therapies and biomarkers (2019)
https://www.thelancet.com/journals/lane ... 1/fulltext

Abstract
2018 has been a year of substantial progress in multiple sclerosis research, with breakthroughs in experimental medicine and translational research. Advances have ranged from successful clinical trials to new reports of promising biomarkers and improved understanding of the pathophysiology of multiple sclerosis.

Excerpts
More than a dozen disease-modifying therapies exist for relapsing-remitting multiple sclerosis, but only one therapy has been approved by regulators to slow progression in primary progressive multiple sclerosis (ocrelizumab), and no therapies have been approved with that specific indication in secondary progressive multiple sclerosis. Ibudilast, a phosphodiesterase inhibitor that crosses the blood–brain barrier, reduced the rate of brain atrophy by about 48% compared with placebo in the
phase 2 SPRINT-MS randomised trial1 of 255 patients with progressive multiple sclerosis, thereby leading the way to a phase 3 trial.
...
Siponimod induced a 21% reduction of the risk of 3-month confirmed disability progression compared with placebo in the
phase 3 EXPAND study2 of 1651 patients with secondary progressive multiple sclerosis.
...
In addition to the progress in treatments for progressive multiple sclerosis and paediatric multiple sclerosis in 2018, a large amount of work has focused on developing new biomarkers for neurodegeneration. Particularly notable are the studies on imaging biomarkers and serum neurofilaments.
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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Leonard » Sun Jan 13, 2019 4:33 am

jimmylegs wrote:
Sat Jan 12, 2019 2:16 pm
Multiple sclerosis in 2018: new therapies and biomarkers (2019)
https://www.thelancet.com/journals/lane ... 1/fulltext

Abstract
2018 has been a year of substantial progress in multiple sclerosis research, with breakthroughs in experimental medicine and translational research. Advances have ranged from successful clinical trials to new reports of promising biomarkers and improved understanding of the pathophysiology of multiple sclerosis.

THIS IS FAKE NEWS GUYS, FAKE NEWS...

In fact they ain't got a clue...

For an improved understanding of the bigger overarching concept, they better look here: general-discussion-f1/topic15188-825.html#p251748
Last edited by Leonard on Mon Jan 14, 2019 3:16 am, edited 4 times in total.

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Sun Jan 13, 2019 4:44 am

it's the lancet. i'm not fussed about the content either, but can we leave this species of discourse to other venues, please and thank you.
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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Leonard » Mon Jan 14, 2019 12:28 am

jimmylegs wrote:
Sun Jan 13, 2019 4:44 am
it's the lancet. ....
exactly, the fact that it is The Lancet makes it all the more serious and disturbing. If we can't trust The Lancet, who can still be trusted?

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Mon Jan 14, 2019 3:54 am

ok so now we have vague non-trust messaging, no specifics re your problems with the content, nothing more than your opinion to counter. not impressive.
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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Leonard » Mon Jan 14, 2019 7:07 am

jimmylegs wrote:
Sat Jan 12, 2019 2:16 pm
Multiple sclerosis in 2018: new therapies and biomarkers (2019)
https://www.thelancet.com/journals/lane ... 1/fulltext

Abstract
... Advances have ranged from ... to ... improved understanding of the pathophysiology of multiple sclerosis.
I claim that nothing has improved on the understanding of the pathophysiology.
The deeper underlying mechanisms are not described or understood.
The viral dimension, the epigenetics and the gut, the oxidative stress, relevant terms are not even mentioned.
This article in The Lancet is like most others: contributes nothing to a better understanding of the overarching concept.

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Mon Jan 14, 2019 10:21 am

so you don't like the article's scope. in the interests of constructive response, please list some 2018 academic publications which do address ms progress within your spheres of interest.
please also provide evidence to support your claim re the article's alleged failure to describe progress on understanding MS pathophysiology. to date nobody here has posted details of or voiced an opinion on the relevant 2018 studies.
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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Scott1 » Mon Jan 14, 2019 6:42 pm

Hi,

We might go around in circles here.

To my mind this was the most interesting article (published in "Cell") last year. https://www.cell.com/action/showPdf?pii ... 18)31027-4

The researchers linked the influence of memory B cells with autoreactive CD4T cells in the HLA-DR15 Haplotype (which I'm sure we share). They acknowledge more work needs to be done to see how environmental factors (they nominate EBV, Vitamin D and smoking) influence this relationship. There is a heap of very good research that they reference which should be fodder for good minds like yours.

Regards,

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Leonard » Tue Jan 15, 2019 1:16 am

And this ACTRIMS Forum was most interesting for its new conceptual thinking:

viewtopic.php?f=1&t=15188&p=250234&hili ... da#p248331

Unfortunately, the thinking has disappeared from the radar again...

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Tue Jan 15, 2019 4:01 am

here's a relevant 2018 contribution.

i searched L's 2017 ACTRIMS info:

https://www.actrims.org/forum2017/

for the term 'epst'. epst search delivered this single result:

S4.3 The relationship between Epstein Barr Virus and MS: Arguments for and against
http://forum2017.actrims.org/forum2017/ ... s/S4.3.pdf

from that i used the following search terms in google scholar:
high anti-EBNA-1 titers

which when filtered for 2018 results returned this as the first item:

Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis
https://journals.sagepub.com/doi/abs/10 ... 8517722646

Abstract excerpts:
"This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo (n = 23) over 48 weeks.
...
Conclusion:
High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism."
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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Leonard » Tue Jan 15, 2019 4:59 am

hi jimmylegs,

If you look at some of the links in my above posting (on the ACTRIMS Forum) you may find further rather interesting views and thinking.

Sure, medical technical articles are important. But one may get lost easily in the detail....

When it comes to the pathophysiology of MS and understanding MS, it is all the more important that connections are made, that a total overarching concept is built first.

The ACTRIMS 2017 Forum was an attempt in the right direction. I am convinced that MS can only be 'solved' if we succeed in knitting together a series of interdependent innovations in areas mentioned in the ACTRIMS Forum and my concept on the other thread.

For that it will be necessary to embrace the new insights all at once and relinquish old dogmas. And it will be necessary to overcome the fragmentation and compartmentalization in the medical world.

The almost total absence of initiatives to build a larger picture is most disturbing and disappointing. If you look at Elsevier publishing on MS and related disorders or other articles in The Lancet, the reader gets lost immediately in technical detail while a total overarching concept remains hidden or obscure. I guess that is what explains my frustration and my comments above.

reg,
Last edited by Leonard on Tue Jan 15, 2019 7:46 am, edited 1 time in total.

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Tue Jan 15, 2019 6:00 am

guess so.
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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by Leonard » Thu Jan 17, 2019 7:17 am

I quote from Martin Pall's work on the NO/ONOO- cycle diseases.
ref: https://www.clinicaleducation.org/resou ... -a-review/

If the view proposed in this article can be shown to be correct, then we will be in a new era in medicine. That will be true even if the relevance of this approach is limited to such diseases as CFS/ME, MCS, and FM. If other proposed NO/ONOO− cycle diseases, such as tinnitus, Parkinson’s, Alzheimers, ALS, asthma, autism, and MS, can also be cured by this approach, then the impact on medicine will be comparable to the previous biggest therapeutic breakthrough, the development of wide-spectrum antibiotics.

Is this all delusional optimism? Clearly, we won’t know until we look. But what we do know is that all of these diseases are chronic diseases, with cases of each apparently initiated by stressors that should be able to initiate the cycle. And we have evidence with all of them for important roles of such cycle elements as oxidative stress, inflammatory biochemistry, mitochondrial dysfunction, and excessive NMDA activity. Where they have been looked at, we also have evidence for BH4 depletion and NF-κB elevation. It is difficult to see how these cycle elements could be involved unless the NO/ONOO− cycle or something very similar to it is not central to the etiology of these diseases.

unquote

Martin Pall's view is right and I have built on it in my thread on a new concept for MS. viewtopic.php?f=1&t=15188&start=840#p252810

But his view on the cellular biochemistry need to be augmented with several other dimensions and that connections are made: the viral dimension and SNPs, the EBV B cells and their superoxide generation, the epigenetics and the gut. All these issues were ingredients of the ACTRIMS 2017 Forum.

We must knit all these issues or interdependent innovations together. It is then and only then that we get a complete and highly plausible picture. And then, as Martin Pall says, we will be in a new era in medicine, with an impact on medicine comparable to the previous biggest therapeutic breakthrough, the development of wide-spectrum antibiotics.

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Re: 2019 Review: MS in 2018: new therapies and biomarkers

Post by jimmylegs » Thu Jan 17, 2019 8:41 am

this info might interest you

viewtopic.php?f=27&t=30655

perhaps also the article at the end of this post

viewtopic.php?p=256429#p256429
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