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.