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.