EAN 2021 | Novel biomarkers to predict progression in MS

About disease progression in MS, that’s the second topic of my talk. In my presentation, I will allude on the use of neurofilament lights for disease progression and also the need for novel biomarkers for disease progression. Neurofilament lights, it has shown a relation with disease progression, for example, in clinical worsening but also in using atrophy measures as outcome measures. Over time, NfL can be prognostic. Another prognostic use or maybe monitoring use would be in trials for targeting disease progression. Then, it would be very relevant to know whether someone who has a high level of nerve damage lights at baseline before treatments would be more prone for a treatment effects, for example, because then you can enrich your trials.

But we’re not yet at that stage, I would say so more research is needed for that. In terms of monitoring drug response in progressive MS, the effects are not completely clear and the effects are probably not as strong as what we observed so far in relapsing MS. It might be that NfL is maybe not a prognostic biomarker or the best monitoring biomarker in progressive MS in contrast to the relapse onset MS. Therefore, we need other biomarkers.

For that, we want to undertake several studies. One paradigm that we chose was to study patients that are on the natalizumab treatments. Because in natalizumab, all inflammation is dampened by the treatment because it’s a very aggressive treatment. We think that’s what’s left is then the non-inflammatory components for disease progression. We think that those are likely the best biomarkers for disease progression. At least that should be the axonal components. That’s the hypothesis.

We already performed some studies, for example, using neurofilament lights and also contactin-1, another protein. We observed that the patients, that despite a natalizumab treatment, still had progression. They did not differ in neurofilament light levels, either at baseline or the response in neurofilament light upon treatments so we could not use neurofilament light to predict who, despite of natalizumab treatment still progressed. Because that’s a problem. I have 50% of the patients that are on the natalizumab treatments still show progression. 50% is an estimation.

But we do think that this paradigm of patients that are on their natalizumab treatments is a good idea. We now undertook analysis of proteomics in these patients and the first results are starting to emerge. We did see patients that had a difference. We did see some biomarkers that shows a baseline difference in the patients who were progressing later on than the patients that remain stable or not stable, who did not progress. That’s the first fresh data, and we are further looking into that. Because still that marker, I will show it also in the presentation. It’s not a difference of day and night between the patients that progress and who don’t. Of course, we also have markers that we’re able to implement at clinical practice. So there, you’re looking for huge differences that you can really make a reliable answer for patients.