#ECTRIMS2021 – Nrg-1-treated Immune Cells Can Promote Myelin Repair
Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Oct. 13–15. Go here to see the latest stories from the conference.
A signaling molecule called Neuregulin-1 (Nrg-1) can help restore myelin and preserve nerve fibers by modulating the activity of brain immune cells called microglia, new research suggests.
Since multiple sclerosis (MS) is characterized by the loss of myelin — a fatty substance that surrounds nerve cells like a sheath, helping them send electrical signals more efficiently — the results suggest that Nrg-1 may hold therapeutic value in MS.
“Currently, we are studying and evaluating the efficacy of Nrg-1 as a potential therapeutic for multiple sclerosis,” Hardeep Kataria, PhD, a researcher at the University of Manitoba in Canada, said in a presentation at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held virtually Oct. 13–15.
MS is caused by the immune system launching an inflammatory attack that damages myelin. Current MS therapies work by reducing inflammation, which can effectively delay disease progression, but the approach fails to repair and restore the lost myelin.
“There is a need to develop therapies which may be able to promote myelin repair,” Kataria said in his presentation, “Neuregulin-1 facilitates remyelination by promoting the reparative properties of macrophages and microglia in animal models of multiple sclerosis.”
Nrg-1 is a signaling molecule thought to be involved in regulating inflammation and in promoting remyelination (the restoration of lost myelin).
In a study published last year, Kataria and his colleagues demonstrated that levels of Nrg-1 are reduced in brain lesions of MS patients and in mouse models of the disease. They also showed that treating mice with the signaling molecule delayed the disease’s onset and eased disability progression.
The data presented at ECTRIMS showed that Nrg-1 treatment also led to increased myelin thickness in the mouse models. The researchers found more axons — the long projections that nerve cells use to connect with each other — in Nrg-1-treated mice than in untreated animals, suggesting that the treatment helped to preserve nerve fibers.
“Nrg-1 was able to increase the myelin index and improve remyelination in these animals,” Kataria said. “Our next question was how it is doing it.”
Additional experiments indicated that Nrg-1 was modulating the activity of microglia, a type of immune cell that lives in the nervous system.
The researchers showed that microglia activated in the presence of Nrg-1 had a greater ability to ingest other cells or particles. This process, called phagocytosis, is required to remove the debris resulting from the inflammatory attacks on the myelin sheath, enabling the repair of MS lesions.
Activated microglia cells treated with Nrg-1 also displayed a marked increase in cholesterol secretion. Cholesterol is a fatty substance that plays several important roles in the body, such as helping to maintain the integrity of cellular membranes. It is also a major component of myelin — about 80% of the cholesterol in a healthy adult’s brain is in the myelin sheath. As such, microglia excreting more cholesterol may help to promote remyelination.
The researchers also showed that activated microglia, treated with Nrg-1, secreted signaling molecules that promoted the maturation and development of oligodendrocytes, which are the cells chiefly responsible for making myelin.
“These findings identify a novel mechanism of Nrg-1 in promoting remyelination in progressive demyelinating conditions, and introduces the promise of Nrg-1 treatment as a potential therapeutic strategy for myelin repair and axon preservation in progressive MS,” the researchers wrote.
The study was funded by the MS Society of Canada.