A few years ago we had the comment was will the real MS stand up and the suggestion that there were distinct processes where the immune system enters the CNS to drive the damage and the other process that the damage is caused by immune responses in the CNS calling in the immune system. This concept was based on the view that immunotherapeutics that inhibit relapsing MS do not inhibit progressive MS.
Many people bought this idea…more fool them…the idea was based on quicksand because the logic was false. It is clearly evident that progressive MS responds to treatments that inhibits relapsing MS…yes they may not work well but they do work and this can be seen when you look at lost of hand function or do trials for longer. Also the concept of immune responses starting in the brain verses outside of the brain is impossible to answer simply once you understand that the inside of the brain feeds into the periphery and the periphery has access to the brain… I personally think that there are different mechanisms occurring in MS and they need different treatments but they are inter-related and both mechanisms are there at the beginning and end of MS. Some people argue MS is one disease and I buy this but think there are distinct processes. So companies now want this because you get permission to use a drug for MS you can use it in relapsing and progressive MS. Pharma split it into two because it helped them to get approval to use the drug in MS as an orphan disease, which means the bar for approval is lower and incentivises pharma to develop drugs for conditions with a low number of people affected.
However people are lemmings and follow dogma without question, e.g., MS is just a problem of CD4, Th17 T cells controlled by T regulatory cells for example. These dogmatic ideas are often spun by opinion leaders and are seldom questioned. We now have paper supporting the idea that there are important distinctions
Shirani A, Stuve O. Beyond the Single-Disease Paradigm-Why Distinctions in Multiple Sclerosis Still Matter. JAMA Neurol. 2025 Dec 29. doi: 10.1001/jamaneurol.2025.5068.
So what does this paper say it says “Patient conversations around the diagnosis of multiple sclerosis (MS) are changing. When asked whether a patient has relapsing-remitting MS (RRMS) or primary progressive MS (PPMS), some patients are now being told all forms of MS are the same disease with the same biology, and that traditional phenotypic distinctions are obsolete. (I say give references to this statement because these people would be idiots and lemmings and their patients should be made aware of it…If this is being said simply to make a point.).
Although this view reflects recognition of overlapping mechanisms across the MS spectrum, such messaging overlooks how classical distinctions still communicate prognosis, determine treatment eligibility and insurance coverage, and shape access to clinical trials. Thus, despite the growing interest in describing MS as a single biological continuum or spectrum, the long-standing distinction between relapsing and progressive courses still shapes how the disease is managed and should not be disregarded.
….. The paper talks a lot about PIRA and as you know I challenge the concept that all of PIRA is truly independent of relapse…however the dogma machine is supporting the view. If your neuro is a lemming and believes all this, they are probably a lemming.
Source: multiple-sclerosis-research.org