Healthcare (Commonwealth Union) – Multiple Sclerosis (MS) is a chronic autoimmune disorder that impacts the central nervous system (CNS), encompassing the brain and spinal cord. This occurs when the immune system erroneously targets the myelin sheath, the protective coating of nerve fibers, resulting in communication disturbances between the brain and the body. Ultimately, this may result in irreversible nerve damage and a variety of neurological manifestations.
Multiple sclerosis is a prevalent neurological condition among young individuals, usually diagnosed between the ages of 20 and 50. Although a cure for MS remains elusive, breakthroughs in treatment have markedly enhanced the quality of life for numerous individuals.
For the first time, scientists have uncovered evidence that inflammation—long linked to Multiple Sclerosis (MS)—may actually drive an increase in genetic mutations tied to the disease’s progression.
MS is a chronic neurological condition affecting around 33,000 people in Australia and three million globally. Approximately one in three individuals with MS experience a progressive form of the disease, for which effective treatment options remain limited.
Researchers examined brain lesions commonly seen in MS patients—areas of active or past inflammation that appear as bright spots on MRI scans. They discovered that neurons within these lesions accumulate genetic mutations at a rate 2.5 times higher than neurons in unaffected brain regions.
The study, published in Nature Neuroscience, was led by Associate Professor Justin Rubio, head of the Neurogenetics Group at The Florey Institute.
Associate Professor Rubio indicated that their findings indicate that inflammation in the brains of people with MS appears to trigger mutations in neurons, which could be a key factor in the disease’s progression.
Researchers from The Florey and the University of Melbourne concentrated on somatic mutations—genetic changes that aren’t inherited but develop in cells as a person ages. These mutations can interfere with how a cell functions or even lead to its death.
To investigate, the team analyzed neurons from the brains of 10 individuals with MS and 16 without the condition. Researchers discovered that neurons in undamaged brain areas and in individuals without multiple sclerosis exhibited an average of 17.7 novel mutations year. Conversely, neurons within MS lesions accrued roughly 43.9 mutations every year.
Associate Professor Rubio stated that at the age of 70, an individual accumulates approximately 1,300 more mutations in neurons affected by MS lesions compared to healthy neurons.
Dr. Allan Motyer, the principal author of the study and a bioinformatician, contributed to the research during his tenure at Melbourne Integrative Genomics and the School of Mathematics and Statistics at the University.
“Not only did we find there are more mutations in MS lesions, but they are also of different types to those seen in normal ageing, indicating a distinct molecular process causes mutations in MS,” explained Dr Motyer.
Associate Professor Rubio and her team are building on this important discovery by exploring new treatment options for progressive multiple sclerosis (MS).
Co-author of the study, Professor Trevor Kilpatrick—an Honorary at the University of Melbourne and a practicing neurologist indicated that this research is significant because it’s the first to suggest that inflammation may drive neuron death in MS by accelerating mutations in the genetic code.
“Once we know for certain what molecular disruptions kill the neurons, we hope to find a way to save them, or keep them alive for longer to minimise progressive disease.
“It’s not a treatment for progressive MS yet, but it brings us closer to one.”
The researchers extended their gratitude to MS Australia and to the families who generously donated brain tissue from their loved ones, making this research possible.
The study was a collaborative effort involving scientists from the University of Sydney, BGI-Australia, and the China National Gene Bank.
