Monday, 19 November 2012

Treatment Aims

Whilst we all want a cure, until you get at the cause then it is going to be difficult. It is should be easier to stop damage occurring rather than repair the damage.

For many years we have focused on the immune response and if we look at the genetics of suceptibility it tells us that the immune response is a major player.  

When a damaging immune system gets in the brain it causes relapse. A damaging immune system is present in progressive disease also. However the two types of inflammation are probably different in nature and need different drugs to treat

Does one type of inflammation condition the presence of the other or are they independent of each other. I think the answer to this is that the lymphocyte-type conditions the other glial-type inflammation but with PPMS this second type of inflammation is set in motion very early. In RRMS this takes more time to set in motion, so disability takes longer to develop.


People with RRMS have different trajectories in their disease some worsen faster than others but at some point the glial-type of inflammation, also set in motion early in disease, surfaces and then disease follows a stereotyped trajectory. 

The aim of a DMT is to move that trajectory, by reducing the conditions that set the glial-type inflammation in motion so that the disabilty accummulates later or ideally not at all. 

The current DMT focus on the lymphocyte-immune response only. For RRMSers this can remove/reduce relapses but does not stop progressive MS if treatment is started late in disease course. The question is can it change the slope? Ongoing trials with Tysabri, Gilenja and Sphingolimod should answer this in progressive MS. 

Will lymphocyte-directed immunosuppression alone stop progression. In my opinion the answer is probably going to be no. So unless the drugs do something extra I predict progression will continue, because we need to target neurodegenerative elements of the disease.

 

If we treat agressively and early the hope it that this alone will move the tragectory sufficently such that disease is treated and that the compensation mechanisms that our brain has can deal with MS.

This is potentially good news for people just being diagnosed, assuming that the regulators can see sense and allow people access to the drugs and that the risk of side-effects is acceptable.

However for people with MS, more needs to be done. We need to target the nerve damaging elements of the disease and this requires use of additional drugs or drugs that have additional properties. But giving nerve protectors or repair agents on their own is probably not going to be the best way to stop progression in RRMS and probably early PPMS as both types of inflammation and the rest need to be dealt with.

19 comments:

  1. What treatments are available / in the pipeline to deal with 'glial-type inflammation'?

    How does all this relate to the EBV theory?

    For someone who has had RRMS for 10 years, this all seems pretty grim - i.e. you've taken Avonex for 7 years, but it won't mean a jot in the logn run (you'll still get progressive). Any hope for me (I don't want to get progressively worse in the future)?

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  2. I have similar questions 1 and 2 as the poster above.

    As for progression - I always knew that the drugs available now won't stop me getting progressive but what I didn't know was that obviously the progression starts in the RRMS phase so to say and that the drugs I have been taking obviously don't even SLOW the moment I slip into SPMS because progression just goes on regardless. Perhaps there is even no such thing as RRMS just progressive MS with occasional relapses - is that what you're are trying to say?

    If that is so then I really don't understand why years have been wasted on the development of horribly expensive drugs which obviously target the wrong kind of inflammation!

    I would also like to know why the sudden change of mind in Prof G and you Mouse - surely you must have got access to some trial results etc. to make this so loud and clear now?












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    1. In America, some scientists have renounced the relapsing-remitting definition and simply label it relapsing multiple sclerosis. There simply is no real remission; the disease is always progressive, pathologic brain atrophy a constant.

      In my research, one always felt that primary progressive MSers are the seriously unlucky bunch, having the one branch of multiple sclerosis you really don’t want to get. It’s the most insidious version of MS, comes out of nowhere and doesn’t even give the sufferer a chance to have a moment of reprieve.

      As relapsing MSers, the neurodegenerative damage is not so severe that you can’t function. If neuroprotective compounds reach the market with the next 5 years, then salvage is still achievable. Progression may be slowed and even possibly stopped.

      PPMSers will have to settle for a simple slowing of disability, which is kind of unfortunate. Their disease will always be the neglected version of MS.

      The current DMTs are criminal to say the least. All that money and risk for a reduction in relapses is futile. The NHS needs to do away with them, immediately. They need to go the way of CCSVI, straight to the back of class with eternal detention.

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    2. Sad. Fellow MSers grudge people with RRMS the relief from relapses that DMTs provide

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    3. Exactly! Relief, not anything more. A relief that costs billions pre year and has resulted in many deaths. I agree with Dre. In Dre we trust!

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    4. Re Dr Dre
      I believe his headphones are very popular.

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    5. "In America, some scientists have renounced the relapsing-remitting definition and simply label it relapsing multiple sclerosis".

      If you have a relapse i.e. worsening there is going to be bettering it is still a remission even if it is not back to normal. It is just words and in American, some peole believe in intelligent design.

      "PPMSers... Their disease will always be the neglected version of MS".
      This just so wrong it is not neglected but until something works for progressive MS PPMSers are getting the rough end of the deal.

      Then the im my mind irrational thoughts appear- criminal drugs eternal detention. However I do think the powers that be need to think.

      So we have Dre and VV both with a party of followers, from what I can see both think DMT are waste of time (I disagree) and Dre thinks CCSVI is pants also

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  3. Have you ever had a relapse?
    Have you ever spent months just sitting on the sidelines of life for weeks or months on end?
    Have you ever suddenly lost all control of your bladder or bowels?
    Have you ever suffered almost unbearable nerve pain with no warning?
    Have you ever been unable to walk?
    Have you ever been paralysed?
    Have you ever been hit with double vision without warning, which lasts for weeks?

    This is life with relapses. This was my life before my DMD and I was relapsing every 8 weeks or so. Now, it's one mild relapse every 3 years. I'm' not progressing.

    Surely Professor G and Mouse Doctor and Dr Dre and his minions, surely, if a person is continuously ill, without much time for remission and healing and rehabilitation, then surely that's worth it?
    I think I'm bloody worth it and so does my family.
    Get real. Stop playing with people's worries and anxieties and have a bit of empathy for your readers and patients.
    If you want those of us with RRMS to stay ill - just like the early 1980s, then you have gone nuts.

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    1. Very impassioned and hard to argue with. If DMTs only offer symptomatic relief and don’t control progression, then I’m afraid they’re not fitting of the price. The dangerous side-effects are also not worth the risks. They may be just a very expensive plaster, the costs of which the tax-payer, including working MSers already taking them, has to bear. The costs need to really come down and stay down till they can be proven to stop progression.

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    2. Re 'If you want those of us with RRMS to stay ill - just like the early 1980s, then you have gone nuts':

      Anonymous 7:35: Prof G and Mouse Doctor haven't said DMDs must go.

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  4. What Prof G said over the weekend with uncompromising clarity & proved through more and more studies is actually the declaration of scientific bankrupcy.

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    1. I do not think there was any real clarity it left even me confused, and as to the rest of your statement it is not worth going there

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  5. So was all of the 'hullabaloo' of the weekend re dmt's having no bearing on disease progression merely Prof G doing a little juxtapositioning ? Will we now see a real sales drive re Alemtuzamab on the grounds it needs to be given early and aggressively within 2 years of dx and told we'll have to wait 20/30 years to determine whether it does indeed stop or slow progression?
    Regards.

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    1. I doubt we will see a sales drive; Campath is off the market at it will be at least 2 years before NICE give a ruling on Alemtuzumab. I also doubt the EMA will give the drug a 1st-line license; this is based on how they treated fingolimod and cladribine. The former is essentially 2nd-line and the latter was rejected. Please don't get your hope up too high the EMA, and NICE, has a tendency to disappoint. The only difference is NICE's motives tend to be financial.

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  6. Hullabaloo..I dunno

    Will we see a sales drive...I don't know it depends on NICE first or second line, I would think it should be first line option as should other markedly active drugs.

    We have to wait to see if it stops progression. Yes because there is no other way to know. However you do not work in avoid and other things will materialise.

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  7. Do the DMT cynics have a way out of this catch22:

    -A drug that doesnt stop progression is a waste of money and it shouldnt be prescribed.
    -The only way to know if a drug stops progression is to prescribe it to many patients for many years
    -But we dont know if it reduces progression so it cant be prescribed. It stops relapses but that doesnt count

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    1. Which is why I keep referring to brain atrophy; this is the best surrogate we have of disability progression.

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  8. why do we keep arguing?
    if you don't want it, don't buy it.
    we are surely educated consumers by now....

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