The central problem is that multiple sclerosis is not a single, uniform disorder. It is an immune-mediated disease of the central nervous system in which inflammation, demyelination, axonal injury, neuronal loss and tissue repair can occur at the same time, but in different combinations and at different intensities. Two people assigned the same clinical course may therefore have very different disease mechanisms operating beneath the surface. One may have frequent focal inflammatory attacks visible on magnetic resonance imaging, while another may accumulate disability through slowly evolving neurodegeneration with few obvious relapses.

The relapsing–remitting category illustrates this limitation. It generally describes patients who experience episodes of neurological dysfunction followed by periods of partial or substantial recovery. However, clinical recovery does not necessarily mean that the disease has become biologically inactive. New lesions may develop without symptoms, and damage can accumulate silently between recognized relapses. Conversely, some symptoms may reflect residual injury rather than a new inflammatory event. The label captures the visible pattern of illness, but not always the activity taking place in the brain and spinal cord.

The transition to secondary progressive multiple sclerosis is also more gradual than the terminology suggests. In practice, worsening disability may emerge slowly, fluctuate from year to year or become apparent only after the effects of repeated inflammatory injuries have accumulated. The precise point at which a patient moves from a relapsing pattern to a progressive one can therefore be difficult to define. Primary progressive multiple sclerosis, meanwhile, identifies people whose disability increases from the outset, but it does not necessarily describe a single biological pathway. Progressive disease can involve varying contributions from inflammation, compartmentalized immune activity, mitochondrial dysfunction, synaptic damage and failure of nervous-system repair.

The roadmap proposes that future descriptions should reflect this multidimensional reality. Instead of treating disease course as a fixed sequence of named stages, clinicians could describe multiple sclerosis through continuously updated dimensions, including inflammatory activity, progression independent of relapse activity, and the degree of disability or neurological impairment. Such a framework would recognize that inflammation and progression are not mutually exclusive. A patient may have active new lesions while also experiencing gradual worsening, or may show disability progression with little evidence of conventional inflammatory activity.

This shift would require more than changing terminology. Biologically informed descriptions would depend on increasingly sensitive measurements that can detect disease processes before they become obvious in routine neurological examinations. MRI already provides information about new or enlarging lesions, contrast enhancement, brain-volume loss and damage in the spinal cord, although these measures do not capture every aspect of pathology. Fluid biomarkers, including molecules associated with axonal injury and glial activation, may offer additional insight into ongoing tissue damage. Digital assessments of walking, hand function, vision and cognition could also reveal subtle changes that are missed during intermittent clinic visits.

A dynamic system could improve both patient care and research. Clinicians would be able to distinguish ongoing inflammatory activity from disability that continues independently of relapses, potentially supporting more precise treatment decisions. Researchers could select trial participants according to the mechanism a therapy is designed to target, rather than relying primarily on broad clinical categories. This might make it easier to evaluate treatments aimed at preventing progression, protecting neurons, restoring myelin or modifying chronic inflammation—goals that are difficult to assess when all outcomes are reduced to relapse counts or a single disability scale.

The proposed transition also carries important practical challenges. New descriptors would need to be reliable across hospitals, countries and patient populations, and they would have to remain understandable to patients and healthcare professionals. Biomarkers must be validated, standardized and shown to provide information that changes clinical decisions. Any new framework should avoid creating a more complicated classification that simply replaces one set of rigid labels with another. It must also account for differences in age, disease duration, treatment exposure, comorbidities and access to care, all of which can influence how multiple sclerosis appears clinically.

The roadmap therefore presents evolution rather than an overnight replacement of the current system. Existing relapsing and progressive terms remain useful for communication and for interpreting decades of research, but they may increasingly be supplemented by biological and clinical descriptors that are updated over time. The long-term goal is a living profile of each patient’s disease, combining symptoms, disability, imaging, biomarkers and treatment response. Such a profile could bring medical language closer to the biology of multiple sclerosis—and help move care toward earlier detection, more precise intervention and a clearer understanding of why the disease follows such different paths in different people.

Subject of Research: Multiple sclerosis disease course and the development of biologically informed clinical descriptors

Article Title: Towards a biologically informed description of multiple sclerosis disease course — a roadmap for transition

Article References: Thompson, A.J., Lublin, F.D., Rechtman, L. et al. Towards a biologically informed description of multiple sclerosis disease course — a roadmap for transition. Nature Reviews Neurology (2026). https://doi.org/10.1038/s41582-026-01249-0

Image Credits: AI Generated

DOI: 10.1038/s41582-026-01249-0

Keywords: multiple sclerosis, disease progression, relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, neuroinflammation, neurodegeneration, biomarkers, MRI, precision medicine

Katrina Adams, a neurobiologist renowned for her work in neurodegeneration, is leading investigations that delve into myelin’s critical role within MS progression. Myelin functions much like the insulation around electrical wires, safeguarding and ensuring the efficient transmission of electrical impulses along axons. The degradation of this fatty layer precipitates the formation of distinct lesions scattered across the central nervous system. These lesions vary not only in size and number but also in their anatomical distribution, resulting in a multifaceted disease pathology. Understanding how these lesions develop and respond to injury is crucial for developing effective therapies.

Research in progressive MS is hampered by the difficulty of acquiring viable human tissue samples, especially from patients in advanced stages. To circumvent this challenge, Adams’ team utilizes preclinical biological models that replicate aspects of MS pathology. Their latest study, recently published in the prestigious journal Nature Communications, undertakes a comprehensive, empirical comparison of two dominant mouse models used in MS research: cuprizone (CPZ) and lysophosphatidylcholine (LPC). Through this comparison, the team advances a more nuanced framework for studying myelin loss and repair mechanisms.

While CPZ and LPC models are both employed to simulate demyelination, their pathological timelines and lesion presentations differ markedly. The CPZ model induces a widespread and gradual loss of myelin over several weeks, providing a systemic perspective on demyelination and remyelination processes. In contrast, LPC produces localized lesions acutely, with rapid myelin degradation occurring within days. These temporal and spatial differences profoundly affect the cellular and molecular responses within the affected nervous tissue, implications that Adams’ research meticulously elucidates.

Adams articulates that this differentiation between models has significant ramifications for experimental design in MS studies. “If your focus is on the biology of oligodendrocytes—myelin-forming cells—and their response to injury, the CPZ model’s gradual demyelination better mimics chronic stress conditions,” she explains. Conversely, for investigations centered on the immune system’s aggressive reaction to damage, LPC’s rapid, focal lesions provide a superior platform. This carefully delineated guidance reshapes how researchers approach the study of MS pathogenesis.

Beyond contrasting these experimental paradigms, Adams’ work leverages single-cell RNA sequencing technology to map genetic expression patterns within the lesions produced by each model, as well as in human MS tissue samples. This transcriptomic approach exposes the molecular signatures driving demyelination and remyelination, revealing how cellular populations transform amid disease progression. By correlating these profiles with human pathology, the research substantiates the clinical relevance of findings from murine models, strengthening translational prospects.

The genetic analyses unearthed unexpected differences in gene expression among various cell types, particularly within oligodendrocytes and immune infiltrates. These transcriptional variations invite further investigation to decipher whether they play a role in promoting or hindering repair mechanisms. This revelation significantly deepens our understanding of the complex interplay between cellular stress responses and adaptive regeneration in the context of MS, offering new frontiers for therapeutic exploration.

Current MS treatments predominantly target immune suppression to curtail the autoimmune assault on myelin, which inadvertently also damages healthy neural tissue. While this has mitigated flare-ups and slowed progression in some cases, it leaves the critical issue of myelin restoration unaddressed. Adams highlights that the potential for pharmacologic enhancement of myelin regeneration—a ‘holy grail’ in MS research—remains an unmet but promising therapeutic objective.

Understanding the fundamental biology of demyelination, facilitated by nuanced preclinical models like CPZ and LPC, is essential for identifying drug targets that could promote remyelination. Adams emphasizes the strategic necessity of employing the right model to match the specific research question, ensuring that interventions developed in the lab have the highest likelihood of benefiting patients. This precision in research methodology accelerates the translation of bench science to clinical application.

Moreover, the study’s integration of genetic, cellular, and pathological data sets from both murine and human tissues provides a robust framework for identifying biomarkers indicative of disease states or therapeutic responses. Such biomarkers could transform MS diagnosis, prognosis, and treatment personalization. Adams’ multidisciplinary approach exemplifies the converging paths of computational biology, molecular neuroscience, and clinical research in modern biomedical science.

Adams envisions that further investigations into these model systems’ unique genetic landscapes will unravel the molecular triggers initiating and sustaining demyelination and repair. Understanding these triggers at the single-cell level could elucidate why some lesions resolve while others persist, deepening our grasp of MS heterogeneity. This knowledge could ultimately facilitate the design of therapies that not only halt damage but actively restore neurological function.

The implications of this research extend beyond MS alone. Given that demyelination is a pathological hallmark shared across various neurodegenerative and neuroinflammatory disorders, insights from these comparative studies may inform a broader spectrum of neurological diseases. Adams’ study thus represents a pivotal advance in neurobiology, merging rigorous experimental modeling with cutting-edge genomic technologies to illuminate the pathophysiology of demyelinating conditions.

The strategic use of CPZ and LPC models, informed by comprehensive transcriptomic analyses, charts a promising course toward translating foundational research into clinical breakthroughs. By elucidating the intricate dynamics of myelin loss and regeneration, Katrina Adams and her team are pioneering efforts that could redefine therapeutic approaches to multiple sclerosis, offering hope for millions affected by this debilitating disorder.

Subject of Research: Animals

Article Title: A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions

News Publication Date: 18-May-2026

Web References:

• https://doi.org/10.1038/s41467-026-72383-y

Image Credits:
Photo by Michael Caterina/University of Notre Dame

Keywords:
Multiple sclerosis; Biological models; Mouse models; Demyelinating diseases; Nerve tissue