ECTRIMS 2021 | Emerging biomarkers in MS: CNTN1 and GFAP

So regarding contactin-1, we came across it because we were interested in it from proteomic studies a while back. So every proteomic study that we performed, be it in multiple sclerosis, or MS in Alzheimer’s disease, or frontotemporal dementia, we did a couple of them, and we always saw contactin family members popping up. So we decided to study them. And when we developed our kits, we wanted to analyze it in different cohorts like dementia, but also MS cohorts. And for MS, there is literature showing that contactin-1 in the initial axon segment has changed expression, I think it was decreased. So we thought that this could be an interesting candidate also in MS, and it was, in CSF.

And in the next stage, and those are data that I will present also at ECTRSIMS, we observed that it’s also decreased in serum of MS patients. And we see a kind of abnormal pattern in those that progress, despite of natalizumab treatments, compared to those that do not progress. So, especially in the first month of treatment with natalizumab, we see that contactin-1 levels are lower in those that have a worse prognosis, you could say that bluntly. And so we continued with those studies. We measured this also peripheral neurological diseases, where we also see some decrease in peripheral neuropathy, for example, especially those who have contactin-1 antibodies, autoantibodies. And there are other data upcoming, where we also see a massive decrease in contactin-1, but I can’t disclose it yet. It’s a cliffhanger.

And so, and with respect to GFAP, that comes back to neurofilament light where we had good plasma essays, but are also good plasmas for GFAP. And for GFAP, we know, since a long time, that it’s involved in MS. It’s part of the glial scar so it’s relevant, or we thought it could be a relevant feature of the MS pathology that we can measure in blood, hopefully. And that’s the case. There is a lot of literature already showing relations of plasma GFAP or serum GFAP, doesn’t matter which you take, serum or plasma, but the relation between the blood components GFAP with imaging measures, in MS. And that’s also what I will show in my presentation. So it seems to be related to structural brain damage when you measure it in the right way. Maybe the relations are a bit more convincing than for neurofilament light so there can be added value in GFAP.

We seem to see that GFAP has a different relation, when measured in it in serum compared to CSF. So that’s something we want to understand better. Other studies that need to be performed are real prospective studies. And also, we observed that GFAP is elevated in those who are cognitively impaired compared to the cognitively unimpaired MS patients so that’s something we would like to follow up as well. But we need to explore more about it. I do think that we are not there yet. They explain part of the variation so we need additional biomarkers, preferably in blood, to be used as readouts in trials, as well as for natural history prediction, for example. Hopefully, they can function for that as well.