ArchiveNovember 2019

Heart features of fingolimod

As we gear up for the mod wars as a number of S1P1 inhibitors arrive including siponimod and ozanimod, it will be interesting to see how fingolimod fairs. Fngolimod binds to S1P1, S1P3, S1P4 and S1P5 but the new variant bind to S1P1 and S1P5 and so avoid S1P3. This is in part the reason why fingolimod has heart issues and needs to be monitored. This risk is relatively low but needs to be checked...

A treatment for NMO

Not that long ago neuromyelitis optica was called Devics MS but it was split because it seems to have a different pathology and responds to MS drugs differently. It also more commonly presents itself East Asia. One of the features of NMO in some people is the production of an antibody to Aquaporin 4 a water channel on astrocytes. Many years ago I stained brain tissue with an antibody to...

The cost of treating MS

One of my patients recently asked if they could return their tablets back to stock as they had decided not to make the swap as initially planned. Of course, the tablets could not be returned, and it’s a couple of hundreds of pounds down the tube. The patient was not to blame for this. Why should a tablet be worth more than the currency of gold? In fact, unanimously high cost drugs top all...

A lymph gland biopsy, Do you think you would do this? It tells us the blood is different

Recently I have had to sit through some dreary EAE studies, where the animal studies were justified by saying it was impossible to know what happens in lymph nodes and bone marrow. in humans I would say do some reading and you will find that the animal studies added nothing to what we know happens in humans. Learning from other autoimmunities to understand targeting of B cells to control multiple...

Pregnancy and Iv Ig

Intravenous immunoglobulins for the prevention of postpartum relapses in multiple sclerosis. Horvat Ledinek A, Brecl Jakob G, Jerše J, Ruška B, Pavičić T, Gabelić T, Barun B, Adamec I, Rot U, Šega Jazbec S, Krbot Skorić M, Habek M. Mult Scler Relat Disord. 2019;38:101519.  OBJECTIVES:To evaluate the effect of intravenous immunoglobulins (IVIG) on prevention of postpartum relapses in women with...

We don’t know how CD20 antibodies works…but it is depletion of myelin CD8 T cells?

How does B cell depletion work. The Charcot meeting has given us nothing concrete. Is it the production of regulatory B cells or something else? So to keep on the Charcot theme of B cell therapy Some people say that it is because ocrelizumab/rituximab attacks T cells. In this new study, they look at CD8 T cells and notably myelin reactive T cells. CD8 T cells express more CD20 than other T cells...

“Useless Lives” – the Dark Story of MS and the Nazis

At the start of the UK Disability History Month, let us not forget… By Rachel Horne I never thought I would end up writing the words Nazi and multiple sclerosis in the same sentence.  Then I went to Auschwitz.  After passing under the infamous Arbeit Macht Frei “Work Sets You Free” gate, our group followed the tour guide into Block 5. There inside the dim, low-ceilinged room, I was...

Charcot Today. It’s not all Unknown! Can we stop memory B cells entering the CNS?

The Charot meeting has now kicked off and after the first key talks. I guess I am currently left confused, it’s the T cells, it’s the B cells, its CD8 T cells, it’s, it’s, it’s, it’s…. as Prof Hauser said today…It’s all unknown how B cell therapies work”. It’s all of them. So lots to do. The cells are all involved, but I am not...

Protecting nerves with the -imods. Is there something missing

Fingolimod is a sphingosine-1-phophaste receptor (S1PR) modulator. There are five S1PR. The immune modulating effect is mediated by S1P1R. Siponimod is an S1P1R and S1P5R selective modulator. Fingo also binds to S1P3R (this causes some of the heart related issues) and S1P4R in addition to S1P1R and S1P5R. S1P5R is found on glial cells and it has been suggested that repair and protection can occur...

B cells and MS…”It’s behind you”…Are we looking in the wrong place?

As the countdown to B cell week at Charcot Meeting (a meeting aiming at training young neurologists) occurs, I had a gripe that I had been given a miss as far as this meeting is concerned. I will be sat at home licking my wounds, as young new minds are manipulated and learn all things MS. However, what you learn depends on what you get taught. There are a series of company sponsored symposia at...

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