Aging immune system and progression


This is a review article that you can read if interested

Efficacy of Disease Modifying Therapies in Progressive MS and How Immune Senescence May Explain Their Failure.Manouchehri N, Salinas VH, Rabi Yeganeh N, Pitt D, Hussain RZ, Stuve O.Front Neurol. 2022 Mar 31;13:854390.

The advent of disease modifying therapies (DMT) in the past two decades has been the cornerstone of successful clinical management of multiple sclerosis (MS). Despite the great strides made in reducing the relapse frequency and occurrence of new signal changes on neuroimaging in patients with relapsing remitting MS (RRMS) by approved DMT, it has been challenging to demonstrate their effectiveness in non-active secondary progressive MS (SPMS) and primary progressive MS (PPMS) disease phenotypes. The dichotomy of DMT effectiveness between RRMS and progressive MS informs on distinct pathogeneses of the different MS phenotypes. Conversely, factors that render patients with progressive MS resistant to therapy are not understood. Thus far, age has emerged as the main correlate of the transition from RRMS to SPMS. Whether it is aging and age-related factors or the underlying immune senescence that qualitatively alter immune responses as the disease transitions to SPMS, that diminish DMT effectiveness, or both, is currently not known. Here, we will discuss the role of immune senescence on different arms of the immune system, and how it may explain relative DMT resistance.

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  • Is ms one disease? Is all ms progressive? Is there a significant division of opinion on this? Virtually every trial seems to exclude ppms, which would imply that any self help action is quite likely to be in vain.

    • The pharma industry created MS to be a multi component disease to make it easier for them to get drugs apporved in the first place (This is becuase of orphan drug status) MS as a single entity had too many people so relapsing and primary progressive were separated, it now bites pharma in the bum as they have to do trials in RRMS and PPMS. IS it one disease? It is until it isn’t. At one point neuromyelitis optica as MS called Devics MS, but once aquaporin 4 antibodies was found to be prognositic and that MS drugs did not all work in NMO it was split off. NMO has now been split, so as we find causative pathologies I expect MS will get smaller

      • If I understood you correctly that MS is unlikely 1 disease but a spectrum, they just shouldn’t be categorized into PP and RR?

  • When clinical trials are conducted, why don’t they include all types of MS? It really infuriates me when I see a drug on trial for relapsing/remitting but each time there are NEVER any people with progressive MS on the same trial. Just a small group of 5 would be less infuriating for me and, who knows?, the drug companies might be surprised by the results!

    • When you do a trial you want to see an effect using as little resource as possible. The best way to get a positive result is to have a responsive outcome and a relatively homogeneous population. Otherwise, you take all comers, but it would mean that the trial has to be much bigger cost more and run the risk of failure. For example with a relapsing trial you can get a positive result using gadolinium enhancing lesions, but you can’t use that outcome for all PPMs cases. What do you do?

      A good example is going to be the octopus trials for progressive MS do you want trials in late stage SPMS which is what will probably be planned or would you plan a trial to find a positive response, because one could argue that you can find a positive response when disease is changing most and this would be earlier. Would you lump PPMS and SPMS together? This was done with ibudilast trial and it seems the PPMS groupshowed the response

      • Thank you for replying to my comment. I can see the logic. As a person with SPMS and at 68 years old and a life of seemingly “benign “MS for 20 years, I do become frustrated, from time to time, when I realise that I will never be cured or experience relief from my MS symptoms.

        I have been fairly lucky, in that it is only over the last three years that I have had to use an electric scooter. So, in comparison to many others with MS, I count myself fortunate .

        Nevertheless, I look at all the fortunate younger people with MS with envy sometimes, as they will possibly experience a cure. I sincerely hope so, for their sakes.

  • Chicken or egg?
    Which comes first, ‘progression’ or relepases?
    Ok I know the dogma says relapses first ie SPMS. But that makes no sense in someone with PPMS who then gets a relapse (ticking magic box for ocrelizumab).
    How many people with RRMS or SPMS can retrospectively (btw the retrospectoscope is a most useful medical instrument) recall early signs of progression long before RRMS diagnosis?

    I can, so that makes at least one 😉

  • What about healthy people? do they suffer from it too? How much more progression do pwMS see and how much of this type of progression is related to previous relapses

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