Wednesday, 15 August 2018

Neuroinflammation associated with nerve damage in progressive MS

This study looks at neuroinflammation. Specifically the fact that the development of treatments for progressive MS is hampered by the lack of suitable biomarkers that can accurately detect and monitor intrathecal inflammation (inflammation which occurs within the spinal theca, which is a sac containing the cerebrospinal fluid which provides nutrients and buoyancy to the spinal cord).

Tuesday, 14 August 2018

How big is your need to exercise?

The evidence that exercise and I mean regular exercise is good for you is so overwhelming that it is hard to argue against the science. What I mean by this is that almost everyone accepts exercise as being good for the general population and for people with MS. The downside is that some MSers are so disabled and/or have so much fatigue that they find it difficult to exercise. I am prepared to accept the latter, but I am not prepared to accept this as a reason not to promote/prescribe exercise to the wider MS community. The question I have 'Is how do we get MSers and healthcare professionals (HCPs) to exercise regularly?'




Are you interested in hearing more about what you can do?

My Tibetan Odyssey: In search of Gods in the highest of places



Mountain climbing as an obsession is a selfish endeavor, and there’s just no way to get around that fact
       -Beck Weathers in ‘Left for Dead' on the 1996 Everest disaster.

Monday, 13 August 2018

ProfG on Twitter

You may have realized that the number of posts have dropped to one a day. 

Some people felt that the haphazard way the posts were done was over-loading people. What do you think?

Anyway, you may want to know that ProfG has been tweeting his views, notably on papers, rather than blogging them.  

@GavinGiovannoni 

Do you want sound bites or words of wisdom?
6 hours ago

The consequences of Britain's heatwave for MSers is profound

How are you tolerating the heat? One patient after another in my MS clinic yesterday complained about heat sensitivity, worsening fatigue, pseudo-relapses (heat-induced intermittent symptoms) and difficulty sleeping. How are you coping; do you have any advice for your fellow MSers?

London feeling the effects of global warming.

Sunday, 12 August 2018

Friday, 10 August 2018

Congratulations to Trishna!

The Barts-MS team would like to extend their congratulations to friend of the team, campaigner and ambassador for pwMS, and generally splendid person Trishna Bharadia. Read on to find out more.


Wednesday, 8 August 2018

#ThinkHand - What happened to #ChariotMS ?



Yes, what happened you might ask, and all I can say is: A great deal.

Learning from others CD20 depletion do we need to deplete so often.

Kim SH, Kim Y, Kim G, Park NY, Jang HM, Shin HJ, Hyun JW, Kim HJ. Less frequent rituximab retreatment maintains remission of neuromyelitis optica spectrum disorder, following long-term rituximab treatment. J Neurol Neurosurg Psychiatry. 2018 Jun 21. pii: jnnp-2018-318465

Rituximab, a chimeric monoclonal antibody that selectively targets CD20+ B cells, has exhibited robust efficacy and an acceptable safety profile in neuromyelitis optica spectrum disorder (NMOSD). Previously, we reported that the therapeutic response of B cell depletion varied among 100 patients with NMOSD, which resulted from multiple factors including Fc gamma polymorphism, and that monitoring CD27+ memory B cell appears to improve treatment outcomes via individualised treatment. Our treatment strategy has also proven to effectively prevent relapse at a lower cumulative dose, compared with the fixed maintenance therapy every 6 months. Currently, we have a group of patients with NMOSD who have undergone long-term rituximab treatment for more than 7 years. We found that retreatment interval became significantly prolonged over time when we targeted depletion of memory B cells. Here, we analysed clinical outcomes and changes in B cell reconstitution over time, following long-term repeated rituximab treatment.

What's this got to do with MS, as NMO isn't MS. 


Yep, but both respond to CD20 depletion.

We know that there are antibodies to a number of CNS proteins in NMO , notably to a water channel expressed mainly by astrocytes and to a myelin protein. 

In MS, we know some people have antibodies to nerve proteins, but these are rare.

However in both NMO and MS, the dosing schedule is set at every 6 months. We have shown that this is probably too frequent for some people as in the ocrelizumab phase II extension study there was efficacy despite being on no drug for 18months

Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K.
Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis. EBioMedicine. 2017;16:41-50.

Perhaps Relapses in NMO than MS are more frequent but the authors have shown that if you dose according to memory B cell numbers, then you don't need to dose as frequently and being closer to once a year than once every 6 months

The annualised relapse rate was reduced by 97% and 62% patients became relapse-free after rituximab treatment. Disability improved or stabilised in 98% of patients.

This is likely to be the case with ocrelizumab too so can we learn something from other diseases
 

Tuesday, 7 August 2018

Manipulating endocannabinoids degradation does not lead to good myelin repair

ProfG tweeted "I wonder what the MouseDoctor will have to say about this study? #ResearchSpeak Deregulation of the endocannabinoid system and therapeutic potential of ABHD6 blockade in the cuprizone model of demyelination. https://buff.ly/2vjBmRE "

Monday, 6 August 2018

Was George Wrong? Relapse Matter

When CCSVI was in its hayday, the believers would question the immune theory and trot out the suggestion that having relapses didn't matter.

Perhaps not surprising it they had read the Work from The George Ebers Lab

Sunday, 5 August 2018

Daclizumab, The Final Nail

If the answer was daclizumab, I often wondered "What was the question"
I guess we don't need to contemplate this anymore

Friday, 3 August 2018

Oral Cladribine works better than Beta Interferon

Cladribine inhibts MS, as was shown in the CLARITY trials, but it was also indicated in other trials.

The ORACLE trial was at the first demyelinating event, and the ONWARD trial was comparing cladribine with interferon beta. 

These trials were terminated when the manufacturers decided to can the development of oral cladribine.

Guess what the ONWARD trial showed?

Thursday, 2 August 2018

Antibody-mediated autoimmunity in humans

Is MS an autoimmune disease? I don't definitively know.
Is there autoimmunity in MS? Absolutely yes.

Why do we know this?

Because if we take autoantibodies found in MS and inject them into the brains of animals with sub clinical disease triggered by T cells,  they cause disease.


Wednesday, 1 August 2018

Guest post - Reducing MS misdiagnosis: The MS Lesion Checklist

It is estimated that 5-13% of patients diagnosed with MS do not have MS (Solomon et al, Curr Neurol Neurosci Rep, 2013). As MS prevalence in the US may be as high as 208/100,000 persons (Wallin et al, 2017), this would translate into almost 700,000 cases of MS, of whom as many as 70,000 could be misdiagnosed. 

Q & A August



If you have a question unrelated to the thread this is the place for you

Tuesday, 31 July 2018

Oligoclonal bands: what are they doing?

Oligoclonal bands (OB) are a characteristic hallmark of MS.

They occur from disease onset. But what are they doing?

Monday, 30 July 2018

Guest post: Has the MS Society woken up?

Finally the MS Society is embracing people with progressive MS and mobility issues in a positive way. There will be a walk of one kilometre at the next sponsored walk in Battersea Park on September 2018.



Sunday, 29 July 2018

Sunday Digest

Here are links to a few papers that some of you may find interesting

Saturday, 28 July 2018

Pre-natalizumab vs. after-natalizumab

I view MS as having two eras, the pre-natalizumab era and after-natalizumab era. Natalizumab has been a transformational therapy for so many reasons and this study provides a little more evidence to support this position. 


Friday, 27 July 2018

Guest Post: teenage girls and smoking

Barts-MS often takes in school students for work experience. We ask some of the students to take on small projects and to write reports. One of our research programmes is to prevent MS. Smoking is an important risk factor for developing MS; smokers have an approximately 50% higher risk of developing MS.


A large and increasing problem in the UK is teenage smoking, particularly amongst teenage girls. We, therefore, asked Amy Sankey, one of our work experience students, to explore this issue amongst her peers at her school. 

The following is Amy's survey and report back. We were very impressed with Amy's commitment and attitude and sincerely hope she achieves her aim of getting into her University of choice to study chemistry.  

Thursday, 26 July 2018

Newsflash Medical Cannabis to be Legalised in the UK. The value of People power

Today the UK have announced that they plan to legalise cannabis for medical use and so join the Republic of Ireland, Germany, The Netherlands and Israel.

Therefore, a new treatment option for symptom control and probably progressive MS (yes a neuroprotective) may be coming your way.

Stornoway research day series: Holistic care of MS patients

MS specialist nurse Mhairi Coutts discusses the definition of holistic care. She outlines how to use the concept as part of caring for people with MS. She argues that a holistic, multi-disciplinary approach is essential to meeting the needs of patients and caring for them effectively.





Wednesday, 25 July 2018

Switching from Natalizumab to Fingolimod

People taking natalizumab often have to stop and switch to something else, such as if you are JC virus positive and have been on previous immunosuppression.

You don't want to immunosuppress in case the person has sub clinical PML. 
You don't want to wait too long because disease will reactivate.

What happens if the time interval is only a month between stopping and starting?

NHS constitution. The DrK Update

This post is for anyone who lives (with MS) in or works (neuros & nurses) in England. This relates t a recent post on the NHS constitution

Update: This is a Comment Made by DrK. As many of you don't read comments I thought I would post this.

"Much of what the barrister said should worry neurologists who feel they can stick to the old days, being highly selective in what they tell pwMS, or simply wait and see".

Firstly, in civil cases, it does not have to be demonstrated that *not* prescribing DMT *has led* (without doubt) to deterioration in the individual (the smoking gun concept). What needs to be shown is that - on the balance of probabilities - waiting and seeing has materially contributed *to the risk of deterioration*.

Secondly, this is very much about the duty of care and offering choice that *provided a pwMS fulfils the criteria* for DMT, options *have* to be discussed. Many colleagues may not be aware of the crystal clear implication of this paragraph in the NHS constitution.


Remember. Ignorance of the Rules means you loose.

Tuesday, 24 July 2018

NHS Constitution. Will the law change prescribing habits?

Is this you?
No I mean You!
This post is for anyone who lives (with MS) in or works (neuros & nurses) in England.

Also for any Americans, as I know you like your constitution stories:-)

Stornoway research day series: Treating to a target of NEDA

What is NEDA? Why is it important? Why should healthcare professionals be aiming for it? DrK presents his arguments in this Stornoway research day talk to healthcare professionals.





Monday, 23 July 2018

Inspire, expires: The first breath of the Charcot Project

Is MS a problem caused by a virus?

Is the world flat?


The INSPIRE trial set out to investigate one of these following an anecdote that a person, who had MS but was treated with HIV-inhibiting treatment, did well. 


Was this a fluke or the beginning of a new era in MS research?



Sunday, 22 July 2018

Diagnosis: bigger is not always better

When you have a first demyelinating event, you get a scan to see if there are lesions in time (lesions of different age) and space (lesions in different places). 

Does it matter how big the scanner is?

Saturday, 21 July 2018

The influence of spinal cord volume loss

Although it is not always done, spinal cord imaging may help to see what is in store for your leg function.

Friday, 20 July 2018

How can we create a prevention study in MS? We need your help!

Many of you will have seen the previous post on Preventive Neurology and the new initiative we are setting up to work towards preventing MS. As many of the comments have identified, this is a difficult area to study. We have to find a way to start monitoring people before they develop the earliest signs of MS. 

                  

Thursday, 19 July 2018

We need feedback on our new listeriosis prevention pack - can you help?

We've now developed our listeriosis prevention pack and would like 10 people to test it out and give us feedback to improve it further. 













     


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).