Wednesday, 18 July 2018

Stornoway research day series: Diagnosing and treating relapses

Dr Sarah Martin talks about how to define and treat a relapse in multiple sclerosis, for healthcare professionals working on the Western Isles.




Tuesday, 17 July 2018

Stornoway research day series: Biomarkers in MS

Doc Neuro Gnanapavan discusses biomarkers in multiple sclerosis, to an audience of healthcare workers on the Western Isles. She defines what biomarkers are, and why they are useful for diagnosing and monitoring MS. 





Monday, 16 July 2018

We need your thoughts

The MS Society in the UK is committed to finding treatments for progressive MS, and have ambitious plans to make that happen as quickly as possible.

They have been asking the question
Which existing drugs could help in progressive MS?

Can you help?

Remyelination. Is ivermectin the next great thing or something dangerous?

What do Remyelination, Parasites and Collie Dogs have in common?

Sunday, 15 July 2018

How do CD20-depleting antibodies work..To T or Not to T that is the Question.

As soon as rituximab and then ocrelizumab, which are both CD20 depleting antibodies, were shown to influence relapsing MS, implicating B cells as a target for MS.

We had a flow of papers indicating that T cells express weak amounts of CD20. This view is trotted out time and time again, if you mention B cells as an issue.

These T cells are depleted by rituximab and so the T cell biologists have clung to the idea that rituximab works by depleting T cells.

Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, Baranzini SE, Leppert D, von Büdingen HC. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol. 2014;193:580-586.

Is this a desperate view to cling to? 

I think so

(A) The Tcellers are happy to accept that depleting 5% of T cells (i.e. the CD20+ T cell subsets) inhibits MS, whilst dismissing the fact that 70% depletion of (CD4) has minimal effect. This makes minimal sense to me

(B) However, it is not only CD20 that implicates activity on B cells. 

Do T cells express Bruton Tyrosine Kinase and CD19, because these B cell depleting agents also work in relapsing MS.

The answer is here.

Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016;197:1111-7. 


"These cells display a lower level of CD20 than B cells and lack markers typically found on B cells such as HLA-DR, CD40 and CD19".

"We sorted CD3+CD20+ cells, CD3+CD20 T cells, and CD19+CD20+ B cells from healthy donors to compare their transcript levels of CD3, CD19, and CD20 by quantitative PCR"......they got


Yep the same result, the CD20+ T cells are not going to be hit by CD19-depleting antibodies.

So can the effect of CD19 depleting antibodies be explained via a T cell mechanism?

Maybe its time to think that really CD20 works, because its depleting B cells.

Saturday, 14 July 2018

Stornoway research day series: Using technology to support an MS service

Iain Trayner runs a technology enabled care (TEC) programme on the Western Isles. They research, source funding and roll out digital technology that supports patient care.




Friday, 13 July 2018

Stornoway research day series: Symptomatic problems

Dr Pushkar Shah discusses symptomatic treatments for MS, as opposed to disease modifying treatments. What treatments are out there to alleviate MS symptoms?





Thursday, 12 July 2018

Hunting for Treatments for Progressive MS.

There are a number of initiatives from the multiple sclerosis societies aiming to hunt and test for treatments for progressive MS.

People are screening public data bases to see if they can get ideas for candidates to test.

We will soon have the results of one of these approaches with the delivery of results from the United Kingdom MS-SMART study. This has tested the influence of fluoxitine (sertonin-reuptake inhibitor), riluzole (a glutamate receptor and ion channel blocker) and amiloride (an acid sensing ion channel blocker) in secondary progressive MS.

Fluoxetine was next on the list after Ibudilast but that was tested in the MS-SPRINT trial undertaken in the United States, which has also finished.

However, the MS Societies have not finished and they want to test more. 

So they need: 

(a) An optimum trial design to test the agents and 
(b) the agents.

The pharma approach is to innovate or to innovate to re-engineer existing targets to get a patent and then test.

The academic approach is to repurpose existing generic drugs.

Academia has found candidates should we give them a go?

Wednesday, 11 July 2018

Ask a Question July

If you have a question unrelated to other posts.

This is the place for you
 Pic by MD2 Derwent Water

MRI: A land of confusion?


When patients present with typical clinical and radiological features, MS is not difficult to recognize. However, things are not always what they seem to be at first glance!


Tuesday, 10 July 2018

Early changes in MS

PLoS One. 2018 Jul 6;13(7):e0200254. doi: 10.1371/journal.pone.0200254. eCollection 2018.

Health-related quality of life, neuropsychiatric symptoms and structural brain changes in clinically isolated syndrome.


Monday, 9 July 2018

Guest Post: MS ‘North of The Wall’

Scotland – the land of bagpipes, haggis, lochs and… multiple sclerosis.



By © User:Colin / Wikimedia Commons, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=42803168


Sunday, 8 July 2018

Saturday, 7 July 2018

Disease activation after abortion

We know that pregnancy reduces the risk of attacks.

Likewise we know that you are risk of attacks, after the baby has been born.

So what happens after an adorption?

Nerve transmitter receptor inhibits myelinating cell formation-Block it to get remyelination

The neurotransmitter acetyl choline binds to muscarinic receptors.


Clemastine  is a muscarinic receptor blocker and stimulates remyelination

Benztropine is remyelinating agent that is a muscarinic receptor blocker too. However, these are dirty drugs and bind to many things, meaning the potential for unwanted side effects.

There are five types of Muscarinic receptors M1-M5 

Which ones are the important ones?....Interested? Read On

Friday, 6 July 2018

Preventive Neurology

Avid readers of this blog will have probably noticed that Prof G has been increasingly focusing on new initiatives recently. One of these is Preventive Neurology - as part of this we have received a large grant to set up a Preventive Neurology Unit, based at the Wolfson Institute of Preventive Medicine within QMUL. 



But what does preventive neurology have to do with MS, given that we can’t even be sure as to the cause of MS? And how will this work? 

Thursday, 5 July 2018

NHS@70: postcode prescribing and doing something about it

Today is the NHS' 70th Birthday. Happy Birthday we love you! 



We know you are the best value for money health service in the world and that you try your best with limited resources. We want to pledge our support for you and help you make the next 70 years even better. 


Wednesday, 4 July 2018

MS Brain Health newsletter – June 2018



Dear supporters 
Over the past month, we have presented MS Brain Health research at major conferences in Europe, the USA and Australia and learned more about the experiences of people living with MS in the USA. It has been great to meet some of you in person at these events, and we are pleased to welcome many new supporters!
Consensus standards presented at EAN 2018 
International consensus standards for the timing of key stages in MS care were presented in our focused workshop, Brain Health in MS: a catalyst for a new approach to management, at EAN 2018 in Lisbon this month. Over 150 attendees joined this interactive workshop and gave their responses to the new quality standards.
Professor Gavin Giovannoni, Dr Gisela Kobelt and Professor Jeremy Hobart gave presentations and participated in a lively Q&A session. "The standards should not be used as a means to criticize MS teams, but instead provide an opportunity for every MS clinic to strive for the highest level of care," stressed Professor Hobart.
Read more
Latest MS Brain Health presentations available to download
Professional organizations in Australasia endorse the policy report
MS Nurses Australasia and the MS Neurology subspecialty group of the Australian and New Zealand Association of Neurologists have become the latest professional groups to officially endorse the policy report, Brain health: time matters in multiple sclerosis. We're delighted that these groups have joined our other 46 endorsers.
Revisions to criteria used in the diagnosis of MS
Motivated by recent technological advances and new data on the diagnosis of MS, experts have refined the 2010 McDonald criteria – the widely used diagnostic criteria for MS. The experts hope that the updated criteria will facilitate early and accurate diagnosis of MS.
Read more
New! Dutch translations of short guides
We are delighted to announce that our guide for people with MS and nursing resource are now available in Dutch. Follow the links above, click 'Download' and select your language.

Please do share these resources with your Dutch-speaking colleagues and friends.
You can follow us on Twitter @MSBrainHealth to keep up with the latest news. Thank you for your continuing support!
Gavin Giovannoni, MD

Professor of Neurology and Chair of the MS Brain Health Steering Committee

On behalf of the MS Brain Health Steering Committee: Gavin Giovannoni, Peer Baneke, Helmut Butzkueven, Jodi Haartsen, Jeremy Hobart, Gisela Kobelt, Christoph Thalheim, Tony Traboulsee, Tim Vollmer and Tjalf Ziemssen
 
If this newsletter has been forwarded to you,
click here to subscribe to future issues.

Follow @MSBrainHealth on Twitter
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MS Brain Health activities and supporting materials are funded by grants from Actelion, Celgene and Sanofi Genzyme and by educational grants from Biogen, F. Hoffmann-La Roche and Merck KGaA, all of whom have no influence on the content.

Editorial and administrative support for the MS Brain Health initiative is provided by Oxford Health Policy Forum, a not-for-profit community interest company registered in England and Wales (registration number: 10475240).

Tuesday, 3 July 2018

Antibodies to PEG interferon may affect its action

Int Immunopharmacol. 2018 Jun 27;62:1-6. doi: 10.1016/j.intimp.2018.06.030. [Epub ahead of print]

Interaction of PEGylated interferon-beta with antibodies to recombinant interferon-beta.

Gilli F, De La Torre AL, Royce DB, Pachner AR.

Abstract


Because PEGylated molecules exhibit different physicochemical properties from those of the parent molecules, PEGylated interferonβ-1a (pegIFNβ-1a) may be able to be used with retained bioactivity in Multiple Sclerosis (MS) patients who have previously developed neutralizing antibodies (NABs) to recombinant interferonβ (rIFNβ). Hence, the objective of the present study was to test whether pegIFNβ-1a is less antigenic for NABs in vitro than rIFNβ. Two in vitro assays were used to quantitate NABs in 115 sera obtained from MS patients included in the INSIGHT study: the cytopathic effect (CPE) assay, and the MxA protein induction assay. NABs cross-reactivity was assessed by comparing dilutions of serum with fixed doses of rIFNβ-1a Avonex® and pegIFNβ-1a Plegridy®. NABs were shown to cross-react in both assays. The y-intercept (c), the slope of the line of agreement (b), the Pearson coefficients as well as the Bland-Altman analysis, indicated that there is good level of agreement between NAB titers against the two IFNβ-1a formulations, with both the CPE (c = 0.1044 ± 0.1305; b = 0.8438 ± 0.06654; r2 = 0.587; bias index ± SD = -0.01702 ± 0.6334), and the MxA protein induction (c = 0.08246 ± 0.1229; b = 0.8878 ± 0.06613; r2 = 0.615; bias index ± SD = -0.09965 ± 0.6467) assays. Until further in vivo evidence is established, clinicians should consider the current in vitro data demonstrating NAB cross-reactivity between pegIFNβ-1a and rIFNβ when discussing new treatment options with MS patients.



Monday, 2 July 2018

EBV in the brain

Epstein Barr Virus (EBV) is a herpes virus which is spread by saliva and infects around 95% of us during our lifetimes. In the majority of people EBV infection does not cause prominent symptoms - it may cause a ‘flu-like’ illness which gets better on its own, or it may go completely unnoticed.

Sunday, 1 July 2018

Stornoway research day series: Diagnosing MS

Prof G outlines how a neurologist will go about diagnosing MS. He explains the difficulties in diagnosing it before symptoms appear, and the difficulties neurologists have dealing with "Dr Google".