Scientists say they've uncovered a molecular signal that turns on myelin production in the nervous system.1 While this is a very preliminary study, they say the discovery could provide a new avenue for treating demyelinating disorders, such as multiple sclerosis, which is characterized by damage to myelin and nerve fibers. But there's much more research to do before the findings become a focus for future therapy design.

Insulation for Nerve Fibers
Myelin is a fatty substance that normally engulfs nerve fibers in the brain and spinal cord. It not only protects these nerve fibers, but helps them communicate with each other. When someone gets multiple sclerosis, the immune system goes haywire and attacks myelin, stripping it away. This leaves the nerve fibers vulnerable to damage themselves, which prompts the symptoms seen in people with the disease. No one knows for sure why the immune system targets myelin in this way, but it's been the focus of much research over the past several years.2

Myelin is wrapped around the axons of nerve cells. These are the long, thin connectors on which nerve cells communicate with other nerve cells (conduct electrical impulses) in the central nervous system. Myelin accounts for up to half the weight of the brain. It's also an essential component of the spinal cord, as well as nerves in other parts of the body.

It's been known for more than a century that there are two kinds of axons in the nervous system; one is wrapped in myelin and looks white and the other has no myelin and appears gray.3 Axons with myelin surrounding them transmit messages in the nervous system up to 100 times faster than their non-myelinated cousins, and are critical for proper neurologic function.

A Myelin 'Switch'
In this latest study, scientists at New York University report they've identified the molecular "switch" that turns on the production of myelin. They did this by growing a cluster of nerve cells in laboratory dishes. During this time, they identified a gene called neuregulin (nerr-REG-yew-lin) that initiates the process leading to the production of myelin. The gene sends a signal to specialized cells in the peripheral nervous system which, in turn, start producing myelin.

"We've been studying neuregulins for many years," explained the study's lead investigator, James Salzer, MD, PhD, a professor of Cell Biology and Neurology in the NYU School of Medicine, in an interview with Priority Healthcare. " A number of labs had shown they are very important in the early lineage of both Schwann cells and, oligodendrocytes." Schwann cells and oligodendrocytes are specialized cells that manufacture myelin in different areas of the nervous system (in the peripheral and central nervous systems, respectively), and each has a unique role in that process.

"It was a logical candidate to look at, since it was so important early in the life of those two cell types," he said.

Building on Previous Evidence
Last year, a group of German researchers reported that the neuregulin gene played a role in determining the thickness of the Schwann cell myelin sheath.4 Even earlier, a separate study suggested that a receptor associated with the gene regulated myelin thickness.5 However, it wasn’t known if neuregulin was required to switch on myelin production in these cells, Salzer explained.  This latest study took those previous findings this step further.

In a series of experiments, the New York researchers and their colleagues at Columbia University and elsewhere showed that neurons without myelin do not possess an active neuregulin gene. But those with myelin do have an active form of the gene. In the first experiment, the research team transplanted axons without myelin taken from mouse embryos into lab dishes. They then added the specialized Schwann cells into the mix. They found that the specialized cells sat on the axons, but did not make myelin. This suggested the gene that would normally initiate the process of myelin production wasn't present.

In the next experiment, they inserted the neuregulin gene into the axons without myelin, which then prompted the Schwann cells to start producing it. Thus, it appears the gene is necessary to instruct the specialized cells to begin making myelin.

"These results indicate that levels of [neuregulin], independent of axon diameter, provide a key instructive signal that determines the ensheathment fate of axons," wrote the researchers.

What's Next?
The NYU researchers only looked at the role of neuregulin relative to Schwann cells in this research. Schwann cells reside in the body's peripheral nervous system, and oligodendrocytes are found in the central nervous system.  As a logical next step, the scientists are initiating research to determine whether the gene has the same effect on oligodendrocytes inside the central nervous system, which includes the brain and spinal cord. "We think it's likely," Salzer speculated, at least in a partial sense. "This is an area of active research by a number of labs, including our own."

If that's the case, it may someday be possible to enhance or fix damaged spinal cords and brain tracts that have been damaged by diseases like MS by transplanting or turning on a functioning neuregulin gene in nerve cells.

Can Fixing Neuregulin Make a Difference?
If it is found that neuregulins directly oversee myelin production in the central nervous system, whether a mutation, or abnormality, in the gene might be responsible for failed remyelination after the sheath is stripped away by the immune system, as what's seen in MS, remains to be seen.

"We don't know why remyelination is so inefficient in the central nervous system," Salzer said. "That's an area that is really of considerable clinical importance that a number of groups are working on."

For one thing, the signaling processes that initiate myelin production early in a human's development versus those that spark remyelination following disease-related damage may be somewhat different, explained Salzer. So, even if it's shown that neuregulin regulates initial myelin production, it will also be necessary to separately determine its role in remyelination after it's been damaged.

As such, while it's too preliminary to predict whether neuregulins might be a logical target for future therapy, "it's certainly an important avenue to explore," he stated.

1. Taveggia C, Zanazzi G, Petrylak A et al. Neuregulin-1 type III determines the ensheathment fate of axons. Neuron 2005 Sep 1;47(5):681-694.
2. National Multiple Sclerosis Society. What is Multiple Sclerosis? Available at: http://www.nationalmssociety.org/What%20is%20MS.asp. Accessed September 9, 2005.
3. Matloub HS, Yousif NJ. Peripheral nerve anatomy and innervation pattern. Hand Clin 1992 May;8(2):201-14.
4. Michailov GV, Sereda MW, Brinkmann BG et al. Axonal neuregulin-1 regulates myelin sheath thickness. Science 2004 Apr 30;304(5671):700-3.
5. Garratt AN, Voiculescu O, Topilko P, Charnay P, Birchmeier C. A dual role of erbB2 in myelination and in expansion of the Schwann cell precursor pool. J Cell Biol 2000 Mar 6;148(5):1035-46.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.