It may alarm arachnophobes to learn that their blood contains objects that resemble spider webs, albeit on a much smaller scale. Although these webs, technically known as Neutrophil Extracellular Traps (NETs), play a crucial role in the body’s defense system, scientists have now learned they also contribute to the triggering of autoimmune diseases, including Multiple Sclerosis (MS). A fortunate coincidence has led the discoverers to a potential treatment option, a drug already in clinical trials for other conditions, and now being tested in animals against MS.
Two recent papers have confirmed long-held suspicions the Epstein-Barr virus is ultimately responsible for most cases of MS. However, most people get Epstein-Barr, it's one of the most common human herpes viruses, and only a few develop MS, which leaves a lot of unexplained complexity in between.
A new paper in Nature Communications has identified NETs as a crucial part of the intervening cascade. NETs boost production of Th17 cells, which normally fight bacterial and fungal infections, but are known to go rogue in autoimmune diseases, attacking parts of the body instead. By a stroke of luck, a drug that has good prospects of damping down this behavior is already being investigated for other conditions.
NETs are produced by white blood cells called neutrophils. They look and work like spider webs, catching bacteria and fungal cells, but Dr Anne Bruestle of the Australian National University has helped reveal their dark side. "We found that the NETs cause Th17 cells to become more powerful, which enhances their detrimental effects," Dr Bruestle said in a statement. This explains the previously established association between NET levels and autoimmune diseases.
“It is known a lot of different factors that can enhance Th17 cells,” Bruestle told IFLScience. “What is new in our work is showing the NETs can as well.”
There is often a long gap between the identification of a target for disease treatment or prevention and the finding of a suitable drug. However, in this case, researchers had a lucky break. Professor Christopher Parish, also of the ANU, has led the development of β-methyl-cellobioside sulfate (mCBS), which is currently in trials as a treatment for sepsis.
Dr Bruestle told IFLScience soon after arriving at ANU she attended a talk by Prof. Parish as part of learning about her new colleagues’ work and thought mCBS might also prove effective at controlling NETs rare harmful behavior. "While we cannot prevent autoimmune diseases such as MS, thanks to these types of therapies we hope to treat the condition and make it more manageable for people living with MS," Bruestle said.
Trials of mCBS for MS can to some extent piggyback off the sepsis research. Bruestle told IFLScience it has already passed safety trials with remarkably few side effects. mCBS’s broad anti-inflammatory behavior also means it is also under investigation as a treatment for acute respiratory distress syndrome, which has raised hopes it could be applicable for COVID-19 patients. Although mCBS may not be able to match the effectiveness of COVID-specific drugs such as Paxlovid, there are hopes it could have a role against future variants and newly emerging coronaviruses before targeted drugs become available.
Bruestle and co-authors have yet to publish the results of animal trials of mCBS for MS, but she described the data so far to IFLScience as “promising”.
Exactly how NET activity relates to the underlying genetic and environmental causes of MS, Epstein-Barr included, is not fully known. However, Bruestle told IFLScience “For NETs to be released from neutrophils requires an environmental trigger, such as bacterial infection, hormone imbalance of cytokine production. It’s totally possible that a virus does the same thing.”