New research suggests that a simple sugar – N-acetylglucosamine – could be a biomarker for the development of progressive multiple sclerosis (MS).
MS manifests differently in each person. With the common relapse-remitting variant (RRMS) of MS patients can often go years without symptoms, however, with progressive MS, a patient’s condition deteriorates with no remission.
Now, a team of researchers from the Experimental and Clinical Research Center (ECRC), a joint institution of Charité – Universitätsmedizin Berlin, the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), as well as eleven colleagues from Berlin, Irvine, and Toronto, have found that the simple sugar N-acetylglucosamine, known as GlcNAc for short, could play an important role in the development of progressive MS.
The results have been published in the journal JAMA Neurology.
A new biomarker for MS?
Currently, therapeutic approaches to MS work off the assumption that the immune system is mistakenly attacking the layer of myelin that surrounds and insulates the nerve cells’ long, cable-like branches called axons.
Dr Alexander Brandt, lead author of the study, said: “In progressive MS, neurodegenerative processes steadily multiply and cause more and more neurons in the brain and spinal cord to die. However, we still do not know what exactly causes this disease variant.”
Brant, along with Professor Friedemann Paul from the Experimental and Clinical Research Center (ECRC), and the rest of the team, hope that not only has potential as a suitable biomarker for progressive MS, but could also pave the way for new therapeutic strategies.
Inside an organism, GlcNAc and other sugar molecules attach to proteins on the cell surface in the form of chains – a mechanism known as glycosylation – which controls various cell functions by forming branched structures from these sugar chains.
“We studied 120 subjects from Irvine and were able to show that, in this particularly severe form of the disease, there are significantly lower concentrations of N-acetylglucosamine in the blood serum than there are in healthy people or patients with relapsing-remitting MS,” said Brandt.
Corresponding author, Professor Michael Demetriou of UC Irvine, added: “In another study of 180 patients from Berlin with relapsing-remitting or progressive MS, we also found that low serum levels of GlcNAc are associated with the development of the progressive form of the disease, clinical disability and neurodegeneration.
“This opens up potential new avenues for identifying, at an early stage, which patients are at higher risk of progressive MS and adjusting their treatment accordingly.”
Human studies
In autumn 2020, Brandt, Demetriou, and other researchers working with the then lead author Dr Michael Sy from UC Irvine published a study in the Journal of Biological Chemistry in which they had administered GlcNAc to lactating mice. The team found that the animals passed on this simple sugar, which is also contained in human breast milk, to their offspring. This stimulated primary myelination of the neuronal axons in young animals.
“We also observed in the mouse experiments that N-acetylglucosamine activates myelin progenitor cells, thus promoting both primary myelination and the repair of damaged myelin,” says Brandt. “Our hope is that we can use GlcNAc and the associated glycosylation mechanism to promote myelin repair and thus reduce neurodegeneration.”
An initial Phase I trial has been completed with around 30 subjects, where the scientists investigated the safety of taking GlcNAc in certain doses. If it is shown to be safe, the scientists hope to conduct further studies into GlcNAc’s possible efficacy as an MS therapy.
