Queen’s University Belfast scientists have discovered that specific cells from the immune system are key players in repairing myelin in the central nervous system – a fundamental breakthrough that could revolutionize the treatment of debilitating neurological disorders such as multiple sclerosis (MS) and many demyelinating conditions such as transverse myelitis, neuromyelitis optica spectrum disorder and acute disseminated encephalomyelitis. In all these conditions, the myelin is damaged, and there are immune cells present at many sites of damage in the central nervous system. Myelin is important because without it, nerves are not able to conduct or send signals where they need to go.
The research study, led by Dr Yvonne Dombrowski and Dr Denise Fitzgerald at the Wellcome Wolfson Institute for Experimental Medicine at Queen’s University Belfast, is being hailed as a landmark study in unravelling the mysteries of how the brain repairs damage.
The research breakthrough, which was published in Nature Neuroscience, shows that a growth regulatory protein made by certain cells within the immune system, called regulatory T cells (Treg), triggers the brain’s stem cells to mature into oligodendrocytes, which are cells that repair myelin. What the Fitzgerald group and collaborators have discovered in different settings of myelin damage (including spinal cord and brain tissue), is that this specific immune cell, Treg, is critical for driving efficient repair of myelin. The Tregs accomplish this by producing a protein, CCN3, that triggers immature oligodendrocytes to mature, start producing myelin, and re-wrap nerves.
They studied this using a focal demyelinating mouse model induced by injecting lysolecithin into spinal cord white matter. They confirmed their findings with a second demyelinating model at a different central nervous system site using another drug called cuprizone. Further, in brain slice cultures, they were able to show that Tregs promoted brain tissue myelination and remyelination in the absence of inflammation. The discovery means that researchers can now use this new knowledge to develop medicines which will boost these particular cells and develop an entirely new class of treatments for the future.
Senior author of the study, Dr Denise Fitzgerald from Queen’s, was diagnosed with transverse myelitis when she was 21 and had to learn to walk again. Commenting on the findings, Dr Fitzgerald said: “This pioneering research, led by our team at Queen’s, is an exciting collaboration of top scientists from different disciplines at Cambridge, San Francisco, Edinburgh and Nice. It is by bringing together these experts from immunology, neuroscience and stem cell biology that we have been able to make this landmark discovery. This is an important step forward in understanding how the brain and spinal cord are naturally repaired and opens up new therapeutic potential for myelin regeneration in patients. We continue to work together to advance knowledge and push the boundaries of scientific knowledge for the benefits of patients and society, in a bid to change lives for the better, across the globe.”
Original Research: Dombrowski Y, O’Hagan T, Dittmer M et al. Regulatory T cells promote myelin regeneration in the central nervous system. Nat Neurosci. 2017 Mar 13.