If you are taking alemtuzumab you may be familiar with the idea that alemtuzumab promotes remyelination.
Here we have a new paper saying that by measuring electrical activity of nerves from the eye to the brain they can see remyelination after alemtuzumab treatment.
Masuda H, Mori M, Kuwabara S. Remyelination and neuroprotective effects of alemtuzumab therapy in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2021 Oct:jnnp-2021-326821.
I would say this is nothing new, indeed ProfC/ProfJ from Cambridge has infered the same effect based on the observation that people treated early in their MS appeared to recover function.
Jones JL, Anderson JM, Phuah CL, Fox EJ, Selmaj K, Margolin D, Lake SL, Palmer J, Thompson SJ, Wilkins A, Webber DJ, Compston DA, Coles AJ. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain. 2010 Aug;133(Pt 8):2232-47
This is great but to burst a bubble, I have to ask how does this work?
There are two major problems well three or maybe four….
- Alemtuzumab penetrates the CNS very poorly, so how does it cause remylination if if doesn’t enter the CNS?..OK you may argue abit gets in like the anti-Lingo which is 99.9% excluded from the CNS. However even is some gets int the CNS the next big problem is……..
- Oligodendrocytes don’t express CD52. So how does it directly stimulate repair if CD52 is not present on myelinating cells?
3. Protective autoimmunty, which means myelin reactive autoimmunity promotes repair because they produce nerve survival factors, is a concept created by the immunological mafia to create a controversial-view based on some arguably, dogey EAE and spinal injury data in and around 2010 that could explain the clinical observation. This was put into the main stream immunological world view, as the concept was not questioned. However, if autommunity was all good, why would all treatments that stop immune cells entering the CNS, be a good thing? To be clear I have no problem with the concept of protective autoimmunity, as I see part of inflammation is destroying the infection and repairing the damage, so it is not surprising that you can find T cells that do useful things. But you have to ask about the balance.
4. You can make your own idea up here….etc.
I will have a go at a simplistic argument
My idea is that the recovery after alemtuzumab was shown in people with relapsing disease treated early following disease onset, when repair capacity, such as oligodendrocyte precursors, still being present around MS lesions. Alemtuzumab stops cells entering the brain and therefore oligodendrocyte precursor repair the damage and there is no direct effect. You dont need the repair agent to enter the CNS. Any agent that stops inflammation will allow repair there is nothing special about alemtuzumab. We just need a similar trial study treating at onset when there are compensatory mechanisms.
COI None relevant
General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.