Multiple sclerosis, or MS for short, manifests itself slightly differently in each person – which is why some call it “the disease of a thousand faces”. Perhaps the worst manifestation of MS is its chronic progressive form. Unlike the more common relapsing-remitting variant (RRMS), in which patients are often symptom-free for months or even years, patients with primary progressive disease (PPMS) see their condition deteriorate steadily without remission.
Poorly isolated neurons die
Current therapeutic approaches are based on the assumption that the immune system makes a mistake and leads an inappropriate attack on the layer of myelin that surrounds and isolates the long, cable-like branches of nerve cells called axons. “In progressive MS, neurodegenerative processes multiply regularly and cause the death of more and more neurons in the brain and spinal cord,” says Dr Alexander Brandt, lead author of the study which has now been published in the review. JAMA Neurology. “However, we still don’t know what exactly causes this variant of the disease.”
With Professor Friedemann Paul of the Center for Experimental and Clinical Research (ECRC), a joint institution of Charité – Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine of the Helmholtz Association (MDC), as well as eleven colleagues from Berlin, Irvine and Toronto, Brandt now hopes he has shed more light on the subject. As the team reported in their study, it appears that the simple sugar N-acetylglucosamine, or GlcNAc for short, may play an important role in the development of progressive MS. Inside an organism, GlcNAc and other sugar molecules attach themselves to proteins on the cell surface as chains. This mechanism, known as glycosylation, controls various cellular functions by forming branched structures from these sugar chains.
The sugar molecule could serve as a biomarker
“We studied 120 subjects of Irvine and were able to show that, in this particularly severe form of the disease, the concentrations of N-acetylglucosamine in the blood serum are significantly lower than those of healthy people or patients with MS. relapsing-remitting, “Brandt reports. At the time of this study, the doctor was heading the translational neuroimaging lab of Paul’s Clinical Neuroimmunology Group at Charity. Brandt has since joined the University of California, Irvine School of Medicine ( UCI) as an associate professor of neurology, but remains a guest researcher at Charité.
“In another study of 180 patients from Berlin with relapsing-remitting or progressive MS, we also found that low serum GlcNAc levels are associated with the development of the progressive form of the disease, clinical disability and neurodegeneration. “, adds the corresponding author of the study. , Professor Michael Demetriou of UC Irvine. “This opens up potential new avenues for identifying, at an early stage, which patients are at higher risk for progressive MS and adjusting their treatment accordingly.
Human treatment studies are under development
In the fall of 2020, Brandt, Demetriou, and other researchers working with then-lead author Dr. Michael Sy of UC Irvine published a study in the Journal of Biological Chemistry. They had administered GlcNAc to lactating mice and found that the animals passed on this simple sugar to their offspring, which is also found in human breast milk. This stimulated the primary myelination of neuronal axons in young animals. “We also observed in mouse experiments that N-acetylglucosamine activates myelin progenitor cells, thereby promoting both primary myelination and repair of damaged myelin,” explains Brandt.
The researchers therefore hope that GlcNAc not only has potential as a suitable biomarker for progressive MS, but could also pave the way for new therapeutic strategies. “We hope to be able to use GlcNAc and the associated glycosylation mechanism to promote myelin repair and thereby reduce neurodegeneration,” summarizes Brandt. A first phase I trial not yet published has just been completed with around thirty subjects, where scientists have studied the safety of taking GlcNAc at certain doses. If it turns out to be safe, scientists are hoping to be able to conduct further studies on the possible effectiveness of this simple sugar as a treatment for MS.
This study was funded in part by a grant from the National Institute of Allergy and Infectious Diseases and the National Center for Complementary and Integrative Health as well as the German NeuroCure Cluster of Excellence.