The Blood–Brain Barrier in Multiple Sclerosis: From Dysfunction to Treatment

So I guess in terms of that dysfunction, do we know a lot about the actual mechanisms that cause it? Do we know the cells that are involved, the molecular pathways that are thought to lead to this disruption of this structure?

Yeah, so there are a lot of pathways that are dysregulated.

So research now focuses on really the omics of the blood brain barrier.

So doing a lot of single cell or single nuclear sequencing studies are out there and that show that a number of pathways are dysregulated.

such as endothelial inflammation is of course one of the pathways that pops up as a consequence.

But what you also see in a number of pathways is that the tightness of the barrier is of course dysregulated.

One of the things that also occurs is that, I told you in the beginning, these endothelial cells are really highly differentiated.

So they have these tight junctions and all these type of molecules.

But apparently during the disease process, they undergo a de-differentiation pathway, which may lead to loss of these disjunctions and loss of their specific function.

So there are a lot of molecular studies ongoing on this.

What we also tend to see is that, coming back to your question, it's not only in the beginning of the disease, but it's actually a chronic event.

And I think that is also very important to highlight here, because the omics studies that are ongoing are usually done on post-mortem brain tissue that has been donated by people with MS that have died of the disease.

So they can donate their brain and on these type of brains, a lot of groups are doing excellent research by investigating what are the molecular pathways that are changed in those brains.

And then those people are of course end stage of the disease.

And still then you see that a number of these pathways are dysregulated.

For instance, that the differentiation program, inflammation, What we also tend to see is that there is a sort of formation of new vessels, but those are leaky.

So that's really a process we call angiogenesis or pathological angiogenesis.

So yeah, we learn a lot now on these pathways.

And what is also important, I think, to highlight is that in the development of MS, the immune cell infiltration is very apparent in the white matter.

And that's also what you see, of course, in the scans.

You see a lot of focal lesions.

But mind you, also the blood main barriers changed in the grey matter.

And that may also lead to cognitive problems and cognitive deficits that you also see in people with MS.

And figuring that out, that's very important, I think, to see what are the drivers and are these the same pathways that are dysregulated in grey matter versus white matter lesions.