Multiple sclerosis (MS) is a debilitating inflammatory autoimmune disease that affects the central nervous system (CNS). While sufferers can experience long periods of remission where common symptoms such as motor control and fatigue can subside as MS lays dormant, increasingly damaged nerves can make the relapses more frequent and severe.
While a lot of treatment for MS is lifestyle-based, or cortisone to suppress the inflammation that causes debilitating flare-ups, there has been limited successful research in cell therapy, and so far there are no therapeutics that promote repair of the damaged nerves.
German researchers out of the Department of Neurology with Clinical Neurophysiology and the Institute of Clinical Biochemistry at the Hannover Medical School (MHH) have instead turned their attention to repairing the sheaths around these nerves by amping up a mechanism regulated by a naturally occurring sugar compound.
In MS flare-ups, rogue immune cells, in response to signals from the brain’s microglial cells, destroy protective myelin sheaths around the nerves, damaging them. A naturally occurring sugar – polysialic acid – plays an important role on activating microglia. The researchers discovered that if they manipulated the microglia cells with added polysialic acid, the cells could switch from being inflammatory to anti-inflammatory, allowing for those nerve sheaths to repair.
"The microglia has an immune receptor called Siglec-E that recognizes polysialic acid," said biochemist Hauke Thiesler from MHH). "The microglial cells are the key cells that do the work directly on site and which we want to guide in a certain direction, so to speak, with the help of polysialic acid and thereby program them for healing.”
The aim is to create an environment that allows those myelin sheaths and nerve cells to repair, alleviating MS sufferers of the many brain and spinal cord dysfunctions associated with the autoimmune disease.
“Those affected are usually 20 to 40 years old when clinical symptoms of MS first appear," said Lara-Jasmin Schröder from the Department of Neurology with Clinical Neurophysiology.
Because of this, the researchers say it leaves a big window for treatments that could encourage self-healing to potentially keep MS in remission almost indefinitely. While preliminary and with results based on a mouse model, the researchers are confident that their significant results can translate to human studies.
"The advantage is that the Siglec-E receptor in the brain actually only sits on the microglia cells, and the polysialic acid can therefore intervene there in a very targeted way," said Thiesler.
There’s also potential to look at other neurodegenerative diseases, given that this therapy acts on a mechanism that turns inflammation to an anti-inflammatory repair zone.
The research was published in the journal Frontiers in Cellular Neuroscience.
Source: Hannover Medical School
