Disability Progression in MS, NMO and MOGAD: from bench to bedside

The study of disability progression, including progression independent of relapse activity (PIRA), in multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is crucial for improving patient outcomes and developing targeted therapies. These disorders share a common feature of neuroinflammatory and neurodegenerative processes, but they differ significantly in their clinical course, pathophysiology, and response to treatment. Understanding the mechanisms behind disability progression in each condition is key to tailoring therapeutic strategies and predicting long-term outcomes.
In MS, disability accumulation can occur due to both relapses and PIRA, where neurodegeneration occurs even in the absence of clinical relapses. Studying PIRA is essential as it reflects the underlying smoldering inflammation and neurodegeneration that continue despite immunomodulatory treatment. Early identification and intervention in patients at risk of progressive disability could significantly alter the disease trajectory.
Similarly, while NMOSD and MOGAD are traditionally viewed as primarily relapse-driven diseases, emerging evidence suggests that some patients experience progressive disability even outside of acute attacks. Investigating the factors contributing to this progression, especially in PIRA-like patterns, can help distinguish subgroups of patients who may benefit from different therapeutic approaches. Moreover, identifying biomarkers that signal early progression can facilitate personalized treatment and improve long-term quality of life.
By studying disability progression and PIRA in these three diseases, we can better understand the shared and distinct pathways of neurodegeneration,
which will aid in developing more effective, disease-specific treatments. This knowledge is also essential for designing clinical trials that more accurately assess treatment efficacy in preventing disability accumulation across the spectrum of these disorders.