Unveiling the Mystery of Progressive Multiple Sclerosis: Unique Brain Cells Identified

Strategic Insights -

Researchers at the University of Cambridge, UK, and National Institute on Aging, US, have made a groundbreaking discovery in understanding the complex mechanisms that drive progressive multiple sclerosis (MS). By reprogramming skin cells from MS patients into induced neural stem cells (iNSCs), they identified a previously unknown type of brain cell, known as radial glia-like cells (DARGs), which are highly specific to MS patients and appear approximately six times more frequently in those with progressive MS compared to controls.

Key Takeaways:

  • The researchers observed that a subset of the cultured brain cells was reverting to an earlier developmental stage, transforming into an unusual cell type known as radial glia-like (RG-like) cells, later designated as disease-associated RG-like cells (DARGs).
  • DARGs exhibit characteristic features of radial glia-specialized cells that serve as scaffolding during brain development, possess the capacity to differentiate into various neural cell types, and function both as structural support and as fundamental building blocks.
  • DARGs display hallmark features of premature aging, or senescence, and possess a distinctive epigenetic profile, with modifications that contribute to an exaggerated response to interferons, the immune system's 'alarm signals,' which may help explain the high levels of inflammation observed in MS.
  • The team validated their findings by cross-referencing with human data from individuals with progressive MS, including new data exploring the spatial context of RNA within post-mortem MS brain tissue.
  • DARGs were found near inflammatory immune cells, supporting their role in orchestrating the damaging inflammatory environment characteristic of progressive MS.
  • The researchers aim to explore the complex interactions between DARGs and other brain cell types, such as neurons and immune cells, to explain the cellular crosstalk that contributes to disease progression in progressive MS.
  • The discovery has the potential to lead to the first truly disease-modifying therapies for progressive MS, offering hope to thousands living with this debilitating condition.

Statistics:

  • Approximately 30% of MS patients experience progressive MS, a phase marked by a steady decline in neurological function with limited treatment options.
  • The new type of brain cell, DARGs, appears approximately six times more frequently in iNSC lines derived from individuals with progressive MS compared to controls.
  • DARGs were found near inflammatory immune cells in 85% of chronically active lesions in post-mortem MS brain tissue.

Sources:

  • Park, B, Nicaise AM & Tsitsipatis D et al. Integrated Multi-Omics Reveals Disease-Associated Radial Glia-like Cells with Epigenetically Dysregulated Interferon Response in Progressive Multiple Sclerosis. Neuron; 10 Oct 2025; DOI: 10.1016/j.neuron.2025.09.022