The clumsiness, blurred vision, and other symptoms of multiple sclerosis have long been blamed on the loss of fatty insulation around nerve fibers. Now scientists report that many of these nerve fibers, called axons, are themselves damaged. The findings, reported in tomorrow's New England Journal of Medicine, help explain why some people develop a severe form of multiple sclerosis (MS) that is practically untreatable and offers a new target for developing treatments for the autoimmune disease.
For many people with MS, neurological symptoms are transient, lasting a few weeks or months. The faulty nerve signaling that underlies the disease is thought to stem from the body's own immune system attacking and degrading the axons' myelin sheaths. Nerves can partially compensate for this damage with an increase of molecular gates called sodium channels. Other patients, however, develop progressive MS with no such remission. This form has puzzled scientists because it cannot be explained by the loss of myelin.
Searching for clues to the origin of severe MS, a team from the Lerner Research Institute at the Cleveland Clinic Foundation in Ohio and Haukeland Hospital in Bergen, Norway, examined brain tissue of 11 people who had been diagnosed with progressive multiple sclerosis. The researchers found severed axons in regions with inflammation characteristic of the disease--in several cases, more than 10,000 times as many cut axons as in brain tissue from non-MS corpses. And once an axon is severed, "the function of that neural cell is lost forever," says the Cleveland Clinic's Bruce Trapp. A high density of severed axons could explain the irreversible nature of progressive multiple sclerosis, he says.
"These are exciting findings that ... could ultimately result in new therapies to prevent worsening in patients with multiple sclerosis," says Stephen Waxman, a neurologist at the Yale School of Medicine. Clinical researchers will now focus on decreasing the inflammation that seems to be the cause of the severed axons and finding new treatments to help preserve the remaining neurons.