Multiple Sclerosis: Much Has Changed; Much More to Do

Author:
Kathleen Costello, MS, ANP-BC
Associate Vice President, Healthcare Access, National Multiple Sclerosis Society

Editor’s note: This flashback commentary is a reflection on the following article from the Consultant archives:

Boines GJ. What can we tell the multiple sclerosis patient? Consultant. 1963;3(4):32-35.

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The landscape of knowledge, research, and treatment of multiple sclerosis (MS) has changed drastically since Consultant ran Dr Boines’ article in 1963. These changes range from earlier diagnosis and better understanding of MS pathology, to a long list of treatment options that can help forestall disease activity and help manage symptoms for many.

Most patients no longer wait agonizing years to get a confirmed diagnosis, thanks to ever-improving criteria for diagnosing the disease with the revised McDonald criteria.¹ We are still awaiting fluid biomarkers that will enable earlier, more accurate diagnoses and guide treatment choices. This is even more critical with recent advances suggesting that MS may begin well before clinical manifestations of the disease.

A large body of evidence supports early treatment of MS with a disease-modifying therapy. Evidence indicates that patients who receive therapy early—or at least within the first 2 years of onset—tend to have less progression of disease than people with delayed treatment. With the advent of therapies that have demonstrated superior efficacy in clinical trials, there is ongoing debate and new research to determine whether induction therapy with a high-efficacy agent or gradual escalation is the better approach for long-range outcomes. And clinical trialists are setting a higher bar with the introduction of the evolving concept of treatment success as NEDA (“no evidence of disease activity”).

There has been an increasing understanding of the immune system players involved in MS. Over the past 35 years, extensive study of an animal model of MS, experimental autoimmune encephalitis, pointed to the adaptive immune system, especially T cells, as a target of immune modulation. However, recent successful treatment of MS with therapies that target B cells (such as ocrelizumab) has broadened the treatment landscape and the scope of research. In addition, the innate immune system is now thought to be playing a destructive role in chronic inflammation.

A profound shift in our understanding of MS pathology has also occurred, and with it a better grasp on what it is going to take to completely stop the disease and reverse its course. I would pin this shift to the pivotal January 1998 study,² by a team led by Bruce D. Trapp, PhD, of the Cleveland Clinic, showing that axonal transection was common in MS brain lesions. This finding provided a renewed understanding of MS as a neurodegenerative disease, and of myelin as not just a passive insulator but a neuroprotective sheath.

Additional bench research and the availability of ever-more advanced magnetic resonance imaging has helped to further uncover underlying disease activity and tissue damage and offer hope for more sophisticated tools to track MS and detect halting of the disease processes and tissue repair.

With the success of immune modulators that can reduce the inflammatory response and limit new damage in relapsing forms of MS, the research focus has been able to pivot toward understanding and finding treatments to address progressive MS. The National Multiple Sclerosis Society launched a global partnership—the International Progressive MS Alliance—that has become a driving force in this arena, funding research and, at the same time, convening thought leaders and building global awareness of this unmet need.

Epidemiological research is uncovering more information about MS risk, with vitamin D deficiency, smoking, childhood and adolescent obesity, and previous infection with Epstein-Barr virus emerging as factors that increase the risk of developing MS.

There is now a much better body of knowledge about MS symptoms and options for addressing them—including cognitive deficits and depression that were not generally recognized 50 or even 30 years ago. There is a growing body of literature on the impacts of comorbidities on MS progression and quality of life, and the possibility that addressing them can reduce the burden of MS symptoms.

“What should I be doing to help my disease?” More and more, my patients are expressing a desire to take charge of their treatment and are asking for advice on wellness approaches to address symptoms—particularly diet and physical activity strategies. There is growing evidence on the benefits of exercise and physical activity, including fatigue reduction, improvement in mood, and improved mobility and endurance. However, there remains a paucity of evidence to enable clinicians to provide in-depth advice on specific exercise and rehabilitation regimens, dosing and frequency to enhance fitness, resilience, and even cognitive reserve. There is less known about specific diets and the potential impact on the MS disease process, although numerous ongoing investigations on various dietary interventions should provide more insight in the coming years.

It is known that the gut microbiome is different in people with MS compared with the non-MS population. Extensive study is ongoing to better understand the microbiome and the impact it may have on the MS disease process. The National Multiple Sclerosis Society supports wellness-focused research to address these and other lifestyle questions.

I’m proud to be able to say that the National Multiple Sclerosis Society has been a catalyst for much of the progress we’ve seen, relentlessly driving research and clinical advances and feeding the intellectual pipeline, including early research investments that led to the approvals of the disease-modifying therapies now available. We have much more to do to fully understand and cure MS, but we’re in a vastly better place for our patients than we were 55 years ago.

REFERENCES:

1. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173.
2. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338(5):278-285.