Sunday, 31 December 2017

Texting and walking: don't forget to self monitor

For soft science of the week, we have texting whilst walking. We know this can be bad for your health, particularly when crossing roads.

Saturday, 30 December 2017

End of Year Revision

As the year draws to a close, it has been a productive year for papers and ideas. 

I predict that during 2018, we will get even more clarity on the story.

But do you believe the academic minnow or the whale?

Friday, 29 December 2017

Reduce your price or else seems to be the message

To follow on from NDG story

Multiple sclerosis - interferon beta, glatiramer acetate (review TA32) [ID809]: Appraisal consultation: 1

The key dates for this appraisal are:
Closing date for comments: 24/01/2018
Fourth appraisal committee meeting: 6 March 2018

Remyelination studies: Publishing the data after pharma has dumped the idea

Positive data for a target for remyelination.

I suspect you are hearing about it after clinical development has been stopped.

Thursday, 28 December 2017

Guest post: Digesting Science makes it to Scotland

We've been trying to get Digesting Science up to Scotland since we started the project. Scotland has one of the highest rates of MS in the world; 11,000 people according to some estimates.

Wednesday, 27 December 2017

What you had to say about coffee and MS

Thank you for completing our recent survey on coffee consumption amongst pwMS and the reasons for drinking coffee. The results are quite interesting. What do you think? 

Tuesday, 26 December 2017

Education: What are B cell follicles?

The lymphatic system is part of the circulatory system and a very important part of the immune system, comprising a network of lymphatic vessels that carry a clear fluid called lymph (from Latin (lympha meaning "water") 

Want to learn more?

NICE and not so nice

Bah, humbug! 

The cynic in me would say would say that NICE (The National Institute for Health Care & Excellence) timed the release of this consultation document in the UK exactly right. Dare I say, an overused political strategy this year has been to shoe it under the door before anyone is the wiser (I won't mention any specifics). And again they will be correct in assuming that over the yuletide, key opinion leaders in MS would either be inebriated, or staving off the first signs of a diabetic coma to take much notice. I don't mind people exercising a bit of stealth when it is required. However, it is the calculated nature by which the process is undertaken that I take umbrage to. It would be a mistake to assume, just simply because their is acquiescence, their is also acceptance.

Monday, 25 December 2017

Can Jesus's Christmas Present stop MS

So a bit of festive research for today

Frankincense is an aromatic resin used in incense and perfumes, obtained from trees of the genus Boswellia

If you believe this stuff, it was brought by the Three Kings to Jesus's birth place, a long time ago.

But can it affect MS?

Happy Christmas

Happy Holidays to all our Readers
Best Wishes from TeamG

Sunday, 24 December 2017

Unusual cases may hold key to understanding

Case reports can off insight into MS, 

B cells at the forefront but does this end of year case report burst the B memory bubble?

Saturday, 23 December 2017

New MOD on the block. Is it too late?

Just as the Nibs are about to enter service here we see another MOD

Friday, 22 December 2017

The 9-Hole Peg Test detects change in Gaming trial

A big beast of the outcome measurement world has criticised our drive for self-assessment and self-monitoring in pwMS. Why? 

Thursday, 21 December 2017

A new B cell drug on the way

Academics are saying "La, La, La, La, La, T cells, T cells, T cells"
and take no notice of our ravings, lucky for you Pharma is not that blinkered.

They can see the value of hitting the B cell and secretly they have been planning on targeting the B cell with some small molecule inhibitors. Want to know more?

Wednesday, 20 December 2017

A revolution: participatory medicine

‘‘Before the Internet, when first diagnosed, I depended on my neurologist. His opinion was the final say about everything from use of steroids to physical therapy to which disease-modifying medicine I would use. The Internet empowered me as a patient to become informed about my condition, to consider my options and the opinions of others, and to take charge of managing my disease in the best possible way for me.’’

How important are the internet and social media to you in managing your MS? 

MS News: too early for a high-dose biotin licence

The EMA has announced that Medday have withdrawn the licence application for high dose Biotin.

The EMA were not convinced by the data presented. 

Tuesday, 19 December 2017

Vitamin D effect in the pivotal fingolimod clinical trials

Chicken or egg? Causation or association (reverse causation)? Is vitamin D a DMT or not? Does this study muddy the waters or provide some clarity? 

Monday, 18 December 2017

PML warning on Cladribine by MHRA.

There has been a warning about the development of PML after the use of cladribine for the treatment of haematological problems issued by the MHRA. Therefore please be vigilant. 

Alemtuzumab stops working. I wonder why?

Alemtuzumab can stop working. Is it because CD4 T cells are no longer depleted or is it because they have neutralizing antibodies?

In some people this occurs, and could be more of a problem after the the second infusion cycle. 

Whats more, some people do not deplete in the first place.

What information do we need to know from the manufacturer?

Sunday, 17 December 2017

A test for MS...Are we there yet?

Wow you said a new study that shows a simple test that can detect MS,

Hailing from “Gods own Country”,  I thought I would Investigate

Saturday, 16 December 2017

DrK's Brain Attack trial

Time is Brain, even in MS! 

How quickly should we treat MS? 

DrK makes the case for treating everyone as quickly as possible. Do you agree? Can you help us convince Biogen about the case for a Brain Attack Trial?

Friday, 15 December 2017

Blockade of Interleukin 17. Is it the Bees Knees?

At a meeting (At the Limits) recently a pair of prominent immunologists took exception, when I hinted that Blockade of Interleukin 17 has been perceived to have failed in MS, because of modest efficacy.

I was challenged on this. I replied I did not say it did not work, but countered that it was not much better than beta interferon. They said that it was not that it did not work, but that it was dropped for operational reasons. 

Operational Reasons. I wonder?. 
Did they simply really mean, it wasn't good enough? 

Thursday, 14 December 2017

Dying on your terms: is it possible?

The Australian state of Victoria has become became the country’s first to legalise assisted dying or suicide. Is dying a better euphemism? 

Wednesday, 13 December 2017

We need a new way to measure upper limb function in MS: can you help us?

As you may know, we at Barts-MS are passionate about the importance of upper limb function for people with MS. And our #ThinkHand campaign aims to increase awareness.

Part of this project is to develop a new way for people to record and measure their upper limb function. We currently work with Patient Reported Outcome Measures (PROMs), such as the ABILHAND, which is a questionnaire that patients are asked to complete at clinical visits.  Read more about that in a previous blog post.

Tuesday, 12 December 2017

Monday, 11 December 2017

Temperature dependence of impulse conduction in optic nerve axons

Thanks for the comments
We were grateful when a number of readers responded to our enquiry regarding temperature dependent symptoms in MS, and we learned more about how people cope with the symptoms. Following this conversation, I thought it worthwhile to draw attention to a paper we recently published, that suggests that there are functional differences between normal peripheral and central axons, and these differences provide a new view on temperature sensitivity.   

Education: What do antibodies do

You have full text access to this OnlineOpen article
Prospects from systems serology research
Kelly B. Arnold and Amy W. Chung
Version of Record online: 1 DEC 2017 | DOI: 10.1111/imm.12861

An internal cell signalling molecule found to support remyelination

Do you want to know about cell signalling and how the oligodendrocyte knows when to make myelin or not?

Sunday, 10 December 2017

Measuring Hand Function

Online monitoring of hand function. Are you up for doing the BRAIN test or will the cardboard 9HPT do the job? 

Saturday, 9 December 2017

Relapse without cell depletion in the blood

As you may be aware I have been banging on about the importance of B memory cells for most of the year, but it has been an uphill struggle to get this view accepted. 

However, response to therapy creates a powerful piece of insight that frankly can't be ignored. But I meet Ostriches ever day.

Friday, 8 December 2017

Fingolimod: does it help with upper limb function?

ProfG G has been been saying that we should #Thinkhand and target hand function for outcomes in clinical trials. This idea may be supported by studies with ocrelizumab and natalizumab but there are a couple of exceptions.

Thursday, 7 December 2017

Reflections on the ECF 2017

I have just returned from the European Charcot Foundation meeting in Baveno, Italy. The meeting is small (< 500 attendees) with no parallel sessions and ample time to mix with attendees and chew the cud. I did a plenary presentation on "dealing with increasing economic constraints".  The feedback I received after my talk, and subsequently via email, has been extraordinary. An eminent neurologist said he was glad that someone was thinking about these issues and taking it on. I have also been contacted by a health economist and have been urged to write up the talk.

Wednesday, 6 December 2017

Yet more data supports the B memory Cell idea

I can hear you saying, "Oh no not another B-cell paper!". However, this is where the action is. It is the B-cell and not the T-cell. Do you agree or disagree? Have your say. 

Tuesday, 5 December 2017

Blood cancers after fingolimod treatment

How immunosuppressive is fingolimod? Does fingolimod's longterm immunosuppression result in an increased cancer risk? 

Monday, 4 December 2017

Guest Post: an update from Saúl Reyes

It has been a while since I last wrote a post for this blog and figured it was time to update you all! I have recently completed my training with Professor Giovannoni and it really confirmed my desire to pursue a career in MS. I am back home in Colombia just getting ready to finish my residency in Neurology. I am incredibly grateful for the time I spent with the Barts and The London Neuroimmunology Group. Every member of the team was very passionate about MS and brought that excitement to teach me. I am delighted to be able to keep in touch with you all through this blog. Please enjoy my new post and don't forget to leave your comments below!

Sunday, 3 December 2017

Danger! Danger! How does the brain sense damage?

The mechanisms which drive inflammation and neuron death in MS are very complicated. These processes involve interactions between multiple cell types in and outside the brain. The crosstalk between nerve cells (neurons), immune cells from the blood, and brain-resident supporting cells (glia) is important to study because it could open up new avenues for disease-modifying therapy. 

Saturday, 2 December 2017

Plasma cells live for a long time in the CNS

Pollok K, Mothes R, Ulbricht C, Liebheit A, Gerken JD, Uhlmann S, Paul F, Niesner R, Radbruch H, Hauser AE. The chronically inflamed central nervous system provides niches for long-lived plasma cells. Acta Neuropathol Commun. 2017 Nov 25;5(1):88

Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma cells also contribute, through secretion of autoantibodies. Long-lived plasma cells are known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, to what extent they are present in autoimmune central nervous system inflammation has not yet been investigated. (Who are they kidding...oh yes the referees) In brain biopsies from multiple sclerosis patients and other neurological diseases, we could detect non-proliferating plasma cells (CD138+Ki67-) in the parenchyma. Based on this finding, we hypothesized that long-lived plasma cells can persist in the central nervous system (CNS). In order to test this hypothesis, we adapted the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to generate a B cell memory response. Plasma cells were found in the meninges and the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling survival niches for these cells, characterized by an up-regulation of chemokines (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In order to determine the lifetime of plasma cells in the chronically inflamed CNS, we labeled the DNA of proliferating cells with 5-ethynyl-2'-deoxyuridine (EdU). Up to five weeks later, we could detect EdU+ long-lived plasma cells in the murine (mouse) CNS. To our knowledge, this is the first study describing non-proliferating plasma cells directly in the target tissue of a chronic inflammation in humans, as well as the first evidence demonstrating the ability of plasma cells to persist in the CNS, and the ability of the chronically inflamed CNS tissue to promote this persistence. Hence, our results suggest that the CNS provides survival niches for long-lived plasma cells, similar to the niches found in other organs. Targeting these cells in the CNS offers new perspectives for treatment of chronic autoimmune neuroinflammatory diseases, especially in patients who do not respond to conventional therapies.

Plasma cells which produce antibody are often found in bone marrow and can live for years but you put them in cell culture and they are dead in a few days. This is because the cells survive in niches where they recieve survival factors from surrounding cells. In this study they track the presence of plasma cells over weeks in animals and suggest that plasma ells survive for some time. I guess we have thought this happens for some time and it is evident that many of the plasma cells in the CNS are not directed to myelin antigens.

The question is what are we going to do?

Have a read if you are interested

The problem here ,is the pictures show the random isolated plasma cell and not B cell follcles

Friday, 1 December 2017

Clinical trial destroys another good idea

McKee JB, Cottriall CL, Elston J, Epps S, Evangelou N, Gerry S, Kennard C, Kong Y, Koelewyn A, Kueker W, Leite MI, Palace J, Craner M.
Mult Scler. 2017 Nov 1:1352458517742979.


Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC).


To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON).


A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18-55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo ( , NCT 01802489).


Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo ( p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer.


Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.
                                     Data from Brain Seq

Amiloride is blocker of ASICS1 channel. This is a neuronal voltage-insensitive sodium channel activated by extracellular protons permeable to Na+, however ASIC1 also shows low Ca2+permeability. It was shown to be neuroprotective in animal models so of we go and do a trial and as we can see as occurred here...the trial fails and animals studies take a beating, like so many other studies.

However I have been arguing that animal studies are not always the problem. I am sorry to say clinicians conspire to mess things up. Sorry but it bursts my bubbles too.

In this study people who had optic neuritis had a month to get on drug. But this is too late as the damage has been done. The damage is done within a few days as we showed in animals, which led to a positive trial when people were recruited and put on treatment within 1-2 weeks as shown in

Raftopoulos, R, Hickman, SJ, Toosy, A. Phenytoin for neuroprotection in patients with acute optic neuritis: A randomised, placebo-controlled, phase 2 trial. Lancet Neurol 2016; 15: 259–269

However, this has chucked away our animal data as this trial was not followed up to change practice such that people with optic neuritis get treated with phenytoin. However I think the amiloride has another problem as it made the nerve transmission slower suggesting that it block remyelination.

It is interesting that oligodendrocyte presusor cells have loads of ion channels on them and this includes ASIC1 (ACCN2) and this drops once cells produce myelin. See the picture. So is this chnnel involved in myelination

Comments, Questions and Answers-December

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

In the past we have done an advent calendar in December, to advertise the Research Day.

However, we do not know about the planning of this, 

So the mice are off on tour.