Multiple sclerosis (MS) is a chronic disease in which the myelin sheath, an insulation that surrounds nerve cells, is slowly destroyed. The causes of the disorder are unclear, but it's thought to be related to immune dysfunction. Scientists have also found links between viral infections and MS, especially Epstein-Barr virus; as well as smoking, obesity, and low vitamin D levels and MS. As MS progresses, neurodegeneration gets worse, and as myelin is lost, the neuronal signals that help our body move and function are disrupted. Researchers have long been searching for ways to halt the loss of myelin, and restore normal myelin, in MS patients.
A new study has investigated the use of gene-editing technologies to repair damaged nerve cells in MS patients. This work used a mouse model to show that cells that boost myelin can be activated with this therapy, leading to the restoration of myelin and improving the conduction of neuronal signals. While more work will be needed before this method can be applied to patients, it has paved the way for better therapeutic options in MS. The research has been reported in Nature Communications.
The investigators focused on brain cells called human oligodendrocyte progenitor cells (OPCs), which can transform into the cells that generate myelin: oligodendrocytes. However, in MS, inflammation and neuronal damage can lead to lesions that disrupt OPCs from differentiating into oligodendrocytes.
The scientists applied the CRISPR gene editing technology to alter a sequence of DNA in OPCs, so they would continue to differentiate into oligodendrocytes regardless of lesions. These genetically engineered oligodendrocytes were then transplanted in the brains of mice. The researchers then observed that myelin repair around neurons was improved.
While this approach has been attempted before, the study authors noted, the MS-caused brain lesions have interfered with the transplanted cells and prevented them from working. This novel approach genetically alters the transplanted cells so they won't be impeded by the lesions, and they repair myelin anyway.
"This is exciting as now we have shown that we can scientifically tweak cells in a dish and transplant them into models to improve repair," said co-corresponding study author Professor Anna Williams of the University of Edinburgh.
Although some MS therapeutics are attempting to tamp down the immune signals that lead to the loss of myelin, this study has tried another approach to repair myelin damage that has already happened.
"Our work is a proof of concept, and the next step is to see if we can remove the need for transplants and edit the cells directly in humans. This is an approach similar to gene therapy which may be an effective method of promoting remyelination in the future," added co-corresponding study author Dr. Laura Wagstaff of the University of Edinburgh.
Sources: University of Edinburgh, Nature Communications