Moving the goalposts

My neuro has confirmed we need to wait to be sure my lymphocytes are safely over 1.0 before initiating any depleting treatment. No doubt wise, but frustrating never the less.

The good thing is that having waited so long, there may yet be a licensed treatment available and off-label treatment might not be necessary after all. Last April phase 3 trial results were published for siponimod:

http://multiple-sclerosis-research.blogspot.com/2017/04/aan-siponimod-phase-iii-positive-in.html

Siponimod is the me-too, younger brother and imroved version of fingolimod. You may recall I had an aborted attempt at starting fingolimod back in summer 2014:

https://annoniemouse1970.blogspot.co.uk/2017/06/2005-in-pre-ms-days.html

I've never paid that much attention to siponimod, assuming it would also be contra-indicated. But, reading more carefully, this drug is selective for activity in the brain and lymph nodes, leaving heart tissue less affected.

So how do the 'imod' drugs work? They are chemical analogues of an endogenous chemical messenger known as sphingosine-1-phosphate (S1P). S1P binds to protein recepters on various cells including lymph nodes, cardiac myocytes (heart muscle) and cells in the CNS (neurones, astrocytes and oligiodendrocytes). The primary treatment effect of fingolimod in RRMS is to trap lymphocytes in lymph nodes and stop them getting into the CNS. A major side effect is bradycardia (slowing of heartbeat), especially after first dose hence you have to be monitored for the first few hours.

The protein recepters on different types of cell vary slightly and have been identified as 5 distinct types. Of particular relevance:

S1P-1   lymph nodes (and CNS cells)
S1P-3   cardiac myocytes
S1P-5   CNS cells             
                                           (over simplified)

Siponimod was found to be S1P-1 and S1P-5 selective in animal models. As S1P-5 has potential for neuroprotection and remyelination, clinical trials followed for secondary progressive MS in 2016 (BOLD phase 2 small study) and 2017 (EXPAND large phase 3 study).

There are, as yet, no treatments licensed for secondary progressive (later stage) MS so this is long awaited.

A letter to my MP

I am 47 years old and have MS. I retired early at age 45 and my mobility is deteriorating. Yet my worst symptom by far is invisible central neuropathic pain. 

I am therefore very moved to have learned today about a lady called Vicky, the exact same age as me, whose MS has taken a most aggressive course:

http://multiple-sclerosis-research.blogspot.com/2018/02/guest-post-argument-for-legalising.html?m=1

hansard.parliament.uk/Commons/2017-10-10/debates/DD48FD3C-C652-4ABB-BE9E-ADDECA878E27/LegalisationOfCanna

I urge you, please, to attend the house on Friday 23 February when this private members biĺl is read and vote to support. 

I would be happy to meet up with you and try to explain first hand the problem of intractable neuropathic pain if that would help.

With kind regards




Ok, it was an e-mail. Probably stands even less chance of being read, let alone acted upon. But this is such a desperate tale, I urge you to do the same. Private members bills notoriously get nowhere, although this one may have a huge weight of public opinion behind it and fare better.

On the up

For those who didn't know, I went to London last week and had the results from my MRI scan from last September. Scan showed lots of lesions in brain but we don't know how long they've been there. None of the lesions were active at the time of scan. Active means catching lymphocytes in action as they push through the blood brain barrier. I understand this can be picked up for 2 to 4 weeks during a typical relapse. So that's good news on one hand, or bad news from the point of view of ticking boxes to qualify for licensed treatments. Had my previous scan from 5 years ago with me, but apparently that's too long ago to usefully  compare with. Seems they keep on the case with yearly monitoring (at least of brain, spinal cord gets left out) up in the big city, down here life pootles on at a slower pace.....
So I now have a baseline scan for future monitoring. New lesions next time have to be from the last year.

In other news, had some more blood tests and am delighted to report that at last, two years post dimethylfumarate (Tecfidera), my total lymphocytes have leapt to a count of 0.9 good news indeed 😁 now waiting for an update to see if at long last I can start on off-label  cladribine injections.