Unraveling Smoldering Multiple Sclerosis and Progressive Disability: Bruce Bebo, PhD

WATCH TIME: 4 minutes

"Even when you have [patients] on these high-efficacy therapies and almost completely suppressing relapses, you still notice this slow progression."

The 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida, spotlights the latest breakthroughs in MS research, with a strong focus on smoldering neuroinflammation, progression independent of relapse activity (PIRA), and innovative treatment strategies. During the Forum, sessions will cover the role of microglial cells in disease progression, the impact of high-efficacy disease-modifying therapies (DMTs), and novel biomarkers for detecting early neurodegenerative changes. As the understanding of MS continues to evolve, additional conversations will center on precision medicine approaches and emerging clinical trials aimed at refining long-term patient care.¹

Over the past decade, research has significantly reshaped clinicians’ understanding of MS, shifting attention beyond relapse-driven disability to the chronic, slow-burning neuroinflammation that persists even in the absence of relapses. This recognition of smoldering MS, driven largely by compartmentalized inflammation and microglial activation, has influenced treatment strategies, with high-efficacy DMTs playing a crucial role in altering disease trajectories. However, despite the success of these therapies in suppressing relapses, slow disease progression remains a challenge, emphasizing the urgent need for treatments targeting nonrelapse-related mechanisms to further optimize patient outcomes.²

Building on this evolving knowledge, 2025 ACTRIMS Forum attendee Bruce Bebo, PhD, executive vice president of research at National MS Society, recently spoke with NeurologyLive^® about the clinical implications of smoldering MS in an interview. He discussed how this concept challenges traditional views on disability progression, highlighting the role of microglial cells in driving PIRA and the importance of targeting compartmentalized inflammation. As researchers continue to explore new therapeutic avenues, Bebo emphasized the need for refining current and emerging therapies to more effectively address this overlooked aspect of MS, paving the way for improved long-term disease management.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Program Agenda. Accessed February 26, 2025. https://forum.actrims.org/program
2. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the 'real MS'. Ther Adv Neurol Disord. 2022;15:17562864211066751. Published 2022 Jan 25. doi:10.1177/17562864211066751