T cell immunotherapy of progressive MS...Time for a rethink or just a think!

Whilst it is with a lot of regret that the ASCEND natalizumab trial has failed in secondary progressive MS. So time for immunosuppressive agents to DESCEND into the bin.

I have to say this is what I predicted before it even started and importantly it is also what EAE predicted too.


Pryce G, O'Neill JK, Croxford JL, Amor S, Hankey DJ, East E, Giovannoni G, Baker D.Autoimmune tolerance eliminates relapses but fails to halt progression in a model of multiple sclerosis.J Neuroimmunol. 2005 Aug;165(1-2):41-52.


An experimental model of secondary progressive multiple sclerosis that shows regional variation in gliosis, remyelination, axonal and neuronal loss. Hampton DW, Anderson J, Pryce G, Irvine KA, Giovannoni G, Fawcett JW, Compston A, Franklin RJ, Baker D, Chandran S. J Neuroimmunol. 2008; 201-202:200-11.

Al-Izki S, Pryce G, Jackson SJ, Giovannoni G, Baker D. 
Immunosuppression with FTY720 (Gilenya)is insufficient to prevent secondary progressive neurodegeneration in experimental autoimmune encephalomyelitis. Mult Scler. 2011; 17(8):939-48. doi:
Hampton DW, Serio A, Pryce G, Al-Izki S, Franklin RJ, Giovannoni G, Baker D, Chandran S.Neurodegeneration progresses despite complete elimination of clinical relapses in a mouse model of multiple sclerosis. Acta Neuropathol Commun. 2013 Dec 23;1:84



Sadly many of my EAE colleagues just stick their head in the ground and say Progressive MS is T cell, T cell, T cell and dismiss anything that does not say T cell, T cell, T cell. 

This is the mantra from many of the big labs in the World. 

Other people have been beaten into submission like some sort of Stepford Wive so they follow the dogma.
The Pryce et al. paper from 2005 had more experiements in true relapsing EAE than any other paper in history, yet our peers didn't want to listen and the paper was rejected by so many journals it was quite depressing. We just had to get it out in the end. 

However, we have been proved right again and again and again.

Do I think that inflammation that can respond  to immunosuppressives in progressive MS.  The answer is yes but we need something in addition. ProfG may also  argue that we need to move away from lower limb mobility to.

So time and time and time again immunosuppressive agents have failed to stop progressive MS, HSCT does not stop progressive MS and so the ultimate immunomodulator fails and so will all the rest. However, people don't listen........or think

How many more trials like this are there going to be?
There are a load ongoing and so prepare yourself for more disappointment. 

Why do they keep doing this? I can only guess. 

I went up to one company person doing a tolerance study in progressive MS at a meeting and said despite them conning themselves that there was a glimmer of hope in the phase II trial data, their phase III was going to fail.  

                   It did and the company is no more.
However, because relapsing-remitting MS is being sewn up by pharma drugs, and unless you are a mega company who can pressurise the regulators to allow you to do a placebo control trial, you can't afford to do a non inferiority against a current MS drug as you will have to buy it at $100,000+ (for 2 years) a person to buy the comparator drug. 

So they go mirror, mirror on the wall, We believe that T cell immunotherapy will cure it all
This allows them to do a placebo control to save a buck, but in doing so they flush their assests down the toilet and their companies into liquidation. 

There will be a few CEOs shedding their shares on this news because they will soon be printed on toilet paper.

Don't blame EAE. Blame the humans.

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