Barry A. Hendin, MD; Regina Berkovich, MD, PhD; and Ahmed Z. Obeidat, MD, PhD, explore the role of biomarkers, precision medicine, and repair mechanisms to improve treatment of MS going forward.
Ahmed Z. Obeidat, MD, PhD: Speaking of clinical trials and the future, Dr Hendin, I’m going to stay with you here. What other future therapeutic interventions are you looking at from a mechanistic approach that are being tested in the pipeline in maybe earlier or later stages, apart from BTK [Bruton tyrosine kinase] inhibitors? What other things do you find interesting?
Barry A. Hendin, MD: If you don’t mind me answering the question slightly askew, you asked about the future as it relates to therapies, and I want to remind us about the future as it relates to diagnosis and markers. One of my great interests is whether we’ll reach a stage of precision medicine, a state of personalized medicine, and whether we’ll develop not just 1 marker, like neurofilament light [NfL] or GFAP [glial fibrillary acidic protein], but a series of markers in a computerized array that allow us to understand prognosis and response to therapy for an individual better, so that we can ultimately achieve this goal of using the right medicine for the right patient at the right time. That’s precision medicine or personalized medicine. That remains one of my great interests. We’re moving in that direction.
The unmet need otherwise is to find a way to repair injury already done in the nervous system. I said probably 6 or 7 years ago when I was engaged in some of those trials that I thought the answer was 5 years off. Those trials haven’t brought a lot of light to date. It’s still a hope for the future. But I think that we’ll be looking at agents that may reduce injury and encourage repair. If you asked me what my long-term hope is, it’s that we’ll understand MS [multiple sclerosis] and the cause of this disease better and therefore can more accurately treat it. It would be wonderful if we had a true antigen and antibody that we could use, but we don’t. It would be wonderful if we had better diagnostics, including newer MRI techniques and better markers, and then earlier diagnosis and prevention and repair. That’s a long answer.
Ahmed Z. Obeidat, MD, PhD: That’s a great answer. Dr Berkovich, what are you most excited about regarding research in MS in the future, therapeutic or diagnostics, or a combination?
Regina Berkovich, MD, PhD: Outcome measures; making sure that we have early responses to whether this particular patient is showing adequate response to treatment, so that if they aren’t, we can move on to a different medication. That’s extremely important. That’s why I’m all for these imaging techniques looking at response to therapy. I agree entirely with Barry that we’re all anxiously looking for the repair mechanisms in MS. Unfortunately, we may not be close to those particular medications being approved. But I’d like to remind our audience that some of our approved medications were looked at to see their ability to promote remyelination in tissue, and they showed that they promote remyelination. That was done for siponimod and alemtuzumab to my knowledge. There are probably more medications that were also studied regarding the same thing.
Adequate treatment of your patient today is the best way to promote repair in an individual person. Don’t think that we don’t have it, and don’t give that impression to the patients. Because the only reason we don’t talk about repair with our available medications is because repair mechanisms weren’t one of the designed outcome measures. But when we look at them in post hoc analysis, like separate studies, tissue-based studies, we see that they show the effect. That’s why patients should be encouraged to remain on effective adequate medication for them because this is the best hope for repair.
Ahmed Z. Obeidat, MD, PhD: These are great points you’re bringing up, that even if we don’t see it, it may still be happening. Maybe we didn’t look for it, or maybe we don’t have the technology to look at it precisely. Maybe it’s happening at a smaller level that we can’t detect at this time. Dr Hendin brought up NfL and GFAP. Maybe those and some of the other biomarkers and nanobiomarkers, the small molecules, we could measure to predict how people are going to do, but also maybe to predict whether they have optimal disease control. That’s where we talk about NEDA [no evidence of disease activity]-5, where you want to look at no evidence of disease activity: no relapses, no progression, no MRI activity, no atrophy in the brain, and also no change in the biomarkers of neural degeneration or neural inflammation. This is what the ultimate goal is, that NEDA-5 is there somewhere, but maybe we’re closer too.
You also mentioned the cause of MS. One of the exciting things is the most recent paper, which is reviving the idea that Epstein-Barr Virus [EBV] may play a major role in developing multiple sclerosis and may be one of the causes of MS. We think there are multiple causes, but EBV might be a leading one of them. This excites me a little also because in some of the pipeline medications or therapeutic approaches, we have the cellular therapies, where T cells are targeting EBV-infected cells. This is another revolution in MS. This is another way we’re thinking of cellular therapy for patients with progressive MS, but we may also be thinking about it in patients with relapsing MS. The research landscape we’re looking at is amazing and looking very bright. With all these studies that we have, we’re going to understand the disease much better. We’re going to probably have more effective interventions and measure the effect of current medications much better. Maybe we’re underestimating the benefit of therapies because we don’t have sensitive tools to measure the response.
Transcript Edited for Clarity