Rethinking Clinical Trial Design and the Immune System in Multiple Sclerosis: Ahmed Obeidat, MD, PhD

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"I want to challenge the concept that the immune system is our enemy in this disease. I want to think of it as maybe as our friend who's just a little bit misbehaving, and we need to put it back in check. We want to redirect the immune system."

Reimagining clinical trial design in multiple sclerosis (MS) has become increasingly important as limitations of traditional efficacy measures, such as relapse rates and MRI lesion activity, have come into sharper focus. Emerging evidence suggests that neurodegeneration and disease progression may continue despite apparent control of inflammatory activity, underscoring the need for end points and therapeutic strategies that prioritize preservation of brain tissue and long-term neurologic function. As understanding of the immunopathology of MS evolves, researchers are reconsidering the role of immune cells not only as drivers of injury, but also as potential mediators of repair and neuroprotection.

At the recently concluded 2026 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 27-29, Charlotte, North Carolina, MS specialist Ahmed Obeidat, MD, PhD, associate professor of neurology at the Medical College of Wisconsin, presented a session titled “Changing the Rules: Reimagining Clinical Trials in Multiple Sclerosis.” In this talk, he explored how conventional paradigms that focus predominantly on immune suppression and inflammatory activity may miss critical aspects of disease biology. His presentation encouraged clinicians and researchers to revisit long-standing assumptions about MS pathogenesis and trial design in light of both historical and contemporary data.

In a follow-up interview with NeurologyLive^®, Obeidat expanded on these themes, describing his effort to “change the rules” around how the immune system is conceptualized in MS. He noted that although the field has shifted emphasis from T cells and macrophages toward B cells, this evolution may risk oversimplifying a complex disease process. He highlighted preclinical and clinical data suggesting that immune cells are major sources of brain-derived neurotrophic factor. Obeidat questioned whether broad early depletion of the immune system might inadvertently deprive the brain of a natural compensatory mechanism. Instead, he proposed a future in which clinical trials are designed to work “with” the immune system.

Click here for more coverage of CMSC 2026.

REFERENCES
1. Obeidat A. Changing the Rules: Reimagining Clinical Trials in Multiple Sclerosis. Presented at: 2026 CMSC Annual Meeting; May 27-29; Charlotte, North Carolina.