A newly identified type of brain cell appears to be a key driver of the chronic inflammation and nerve cell degeneration found in progressive multiple sclerosis, a discovery that opens a new avenue for developing treatments. Researchers found that these rare cells, which are far more prevalent in MS patients, exist in a paradoxical state, reverting to an infant-like developmental stage while also exhibiting signs of premature aging. This unique combination of characteristics leads them to release a cascade of inflammatory signals that damage the surrounding brain tissue.
This finding marks a significant step forward in understanding the relentless progression of this stage of the disease, for which few effective therapies exist. Multiple sclerosis is an autoimmune disorder where the body mistakenly attacks the protective myelin sheath that insulates nerve fibers in the brain and spinal cord. While many patients first experience relapsing-remitting symptoms, a substantial number transition to a progressive phase marked by steady neurological decline. By identifying these specific cells as a source of the persistent inflammation, scientists have a new and promising target for interventions that could potentially halt or slow the disease’s advancement.
A Malfunctioning Cellular Architect
The cells at the center of the discovery are called disease-associated radial glia-like cells, or DARGs. They are a dysfunctional version of radial glia, a specialized type of cell crucial during early brain development. In a healthy, developing brain, radial glia act as a scaffold, guiding the formation of the brain’s structure and giving rise to other essential neural cells like neurons. They are fundamental building blocks that are typically rare in the adult brain.
In patients with progressive MS, however, these DARG cells reappear in significant numbers. The research showed that the biological phenomenon leading to DARGs was six times more likely to occur in the cells derived from MS patients than in those from healthy individuals. Instead of supporting brain health, these cells adopt a destructive role. They appear to be trapped in an abnormal state, partly reverting to their primitive developmental function while simultaneously undergoing senescence, a form of premature aging. This senescent state causes them to secrete molecules that promote a highly inflammatory environment.
Propagating Damage in the Brain
Researchers have determined that DARGs do not just malfunction; they actively contribute to the cycle of damage that characterizes progressive MS. According to Professor Stefano Pluchino of the University of Cambridge, these glial cells “actively spread damage.” The inflammatory signals they release act on neighboring brain cells, pushing them into a state of premature aging as well. This process creates a toxic feedback loop, fueling the chronic inflammation and accelerating the neurodegeneration responsible for the steady decline in function experienced by patients.
To validate their findings, the scientific team analyzed post-mortem brain tissue from MS patients. This examination confirmed the presence of DARGs and revealed their specific location within the brain. The cells were found to be highly concentrated within the borders of chronically active lesions—the precise areas that experience the most severe and persistent damage in progressive MS. Furthermore, the DARGs were located in close proximity to inflammatory immune cells, suggesting a direct role in creating and sustaining the damaging environment that prevents the brain from repairing itself.
Innovative Laboratory Modeling
From Skin Cells to Brain Cells
The breakthrough was made possible through an advanced laboratory technique that involved modeling the disease in a dish. Scientists at the University of Cambridge and the National Institute on Aging collected skin cells from patients with progressive MS. Using modern reprogramming technology, they converted these skin cells into induced neural stem cells (iNSCs), which are immature cells capable of developing into various types of brain cells. This innovative approach allowed the researchers to observe the development of neural cells from MS patients in real time and compare it to cells from healthy donors.
Observing a Cellular Anomaly
As these induced neural stem cells matured in the lab, the researchers noticed the emergence of the unusual DARG cells specifically in the cultures derived from MS patients. This experimental setup was crucial for isolating and identifying the cells responsible for the inflammatory activity. By studying the gene expression patterns at a single-cell level, the team was able to pinpoint the unique epigenetic and molecular signatures of DARGs. They found these cells had unusual epigenetic patterns that boosted their response to interferons, a type of immune signaling molecule, which helps explain the high inflammation levels seen in the disease.
New Hope for Therapeutic Intervention
The identification of DARGs provides a concrete target for the development of new drugs. For years, the precise cellular mechanisms driving the inflammatory and degenerative aspects of progressive MS have remained elusive, hindering the creation of effective treatments. This discovery shifts the focus to a specific cell type that appears to be a central player in the disease’s pathology. Targeting DARGs could lead to the first generation of therapies designed to modify the progressive course of the disease, rather than just managing symptoms or suppressing the wider immune system.
Future therapeutic strategies could focus on several approaches. One possibility is developing drugs that can repair the dysfunctional DARGs, potentially coaxing them out of their inflammatory, senescent state and restoring a more normal function. An alternative approach would be to create treatments designed to selectively eliminate these cells from the brain. By removing the source of the chronic inflammatory signals, it may be possible to break the cycle of damage and allow for natural repair processes, such as the remyelination of nerve fibers, to resume. While this research is still in its early stages, it offers a promising path toward halting the progression of a devastating condition that affects millions worldwide.