Patients with multiple sclerosis (MS) show a substantial spectrum of disease severity, from those with a benign disease course who never acquire significant disability, to those with very aggressive disease from early on. Identifying where a patient lies on this spectrum is important as it impacts the optimal therapeutic approach. Mark Freedman, MSc, MD, CSPQ, FAAN, FRCPC, University of Ottawa & Ottawa Hospital Research Institute, Ottawa, Canada, discusses the importance of categorizing patients, as well as the nature or nurture debate surrounding the behavior of MS. While many believe DNA plays the greatest role in determining MS disease course, durable remission following autologous hematopoietic stem cell transplantation indicates that nature has a significant impact. This interview took place during the ACTRIMS Forum 2021.
Transcript (edited for clarity)
I think this particular lecture fit in with the overall theme of the meeting, which was the spectrum of MS. And the idea that there are some patients who are fortunate and have a rather benign course. And then the other side, there’s those patients who have fairly aggressive early course. And being able to identify them, obviously contributes greatly to your decisions on management. And that’s what I was focusing on was, how best one could identify patients who perhaps are more benign or more aggressive...
I think this particular lecture fit in with the overall theme of the meeting, which was the spectrum of MS. And the idea that there are some patients who are fortunate and have a rather benign course. And then the other side, there’s those patients who have fairly aggressive early course. And being able to identify them, obviously contributes greatly to your decisions on management. And that’s what I was focusing on was, how best one could identify patients who perhaps are more benign or more aggressive. This is not a black and white science. In fact, if anything, it’s gray, but there are features that typify patients who for instance will have a more aggressive course. That’s actually much easier for us as clinicians, is identifying those individuals whose characteristics would imply that they have a higher risk for early progression. And that being the case, you would want to be more aggressive so that your treatment is identifying aggressive disease. You meet it with an aggressive therapy.
The harder group is to identify those who may not have the aggressive type of MS. If it was easy to treat and the medicines and the treatments were safe for everybody, we wouldn’t be having this discussion, because you would just treat everybody with the most powerful thing you have and that would be the end of the story. But unfortunately, with aggressive therapy also comes some fairly significant safety issues. So rather than hit everybody with that, you would want to try to identify those who are more benign and offer them treatments that are effective but safe, and only give them progressive therapy should it be warranted that their disease suddenly changes. So the nature/nurture story is very much, the nature would be your genes. And if your DNA confers your risk for early progression, what are we going to do in our therapies? We’re going to be coming up against mother nature.
And if you’re destined to have a bad outcome, how are we going to necessarily change that? And I hope that I was able to identify the fact that although DNA may confer some things about MS, the fact that we can completely stop the disease in its track with a drastic treatment such as bone marrow transplants, where you replace the entire immune system and the disease stops. If it was all being driven by the genes, all those patients would just start having activity all over again, but they don’t. So clearly the nurture side is I think [inaudible 00:03:13], because we’re able to then offer patients appropriate treatments that maybe are people who believe strongly in the DNA are being proven wrong.
Research or educational grants: Sanofi-Genzyme Canada, Hoffman-La Roche, EMD Inc. (Canada) Honoraria or consultation fees: Actelion (Janssen/J&J), Alexion, BiogenIdec, Celgene (BMS), EMD Inc., Sanofi-Genzyme, Hoffman La-Roche, Merck Serono, Novartis, Teva Canada Innovation Member of a company advisory board, board of directors or other similar group: Actelion (Janssen/J&J), Alexion, Atara Biotherapeutics, BayerHealthcare, BiogenIdec, Celgene (BMS), Clene Nanomedicine, GRI Bio, Hoffman La-Roche, Magenta Therapeutics, Merck Serono, Novartis, Sanofi-Genzyme, Teva Canada Innovation Company sponsored speaker’s bureau: Sanofi-Genzyme, EMD Serono