At the annual Society for Neuroscience meeting last month, I met with Ben Barres, professor of neurobiology at Stanford University, who told me about some of his lab’s latest work on understanding myelination, work that offers hope for treating multiple sclerosis (MS) and related diseases.

Myelin is the fatty sheath that insulates neurons and is required for proper neuronal function. In the brain and spinal cord, cells called oligodendrocytes surround neurons and repeatedly wrap around them – this wrapping is called myelin.

Once an oligodendrocyte is finished wrapping around, or myelinating, a neuron, you’ve got a long, thin neuron surrounded by layers of myelin – much like a thin electrical wire is surrounded by thick insulation.

When that insulation is damaged, through injury or disease, neurological problems arise.

Imagine a mouse chews through portions of the insulation surrounding an electrical wire that supplies power to a lamp. The damage to the lamp depends on how frequently the mouse nibbled along the wire and on the depth of each bite. If the damage to the insulation is mild, the lamp might not be affected at all. Alternatively, the lamp might flicker briefly, or continuously, or the light might appear dim. If the mouse chews through the insulation completely, the lamp might produce no light at all.

De-myelinating diseases work the same way. Substitute myelin for insulation, neuron for lamp and immune response for mouse, and you have MS – a disease where myelin is progressively damaged by the immune system, leading to neurons that don’t function properly.

Frayed neurons are like frayed wires, though instead of powering lamps neurons form connections that are essential for sensation, movement, and thought. Like the mouse nibbling through the wire, the symptoms of MS are unpredictable and wide-ranging in severity, from double vision to a tingling sensation in the limbs to complete loss of feeling and movement. There is no cure and no effective treatment.

The brain does have the ability to repair damaged myelin to some extent, but invariably the disease strips myelin faster than it can be repaired.

Researchers are working to understand the molecules involved in myelin formation, maintenance and repair, in the hopes of treating MS and other demyelinating disorders.

A big problem in the field has been the lack of a good cell culture system in which to study myelin. Animals are complex, so scientists often study biological components in isolation. Growing cells in a dish is a common technique, however nobody has been able to get oligodendrocytes to myelinate neurons like they do in an animal.

Trent Watkins, a graduate student in Barres’ lab, has a solution. Using oligodendrocyte precursor cells (the cells that will mature into oligodendrocytes and produce myelin) from rat or mouse brains and neurons from the optic nerve in rats, he came up with a way to culture them in a dish such that the precursor cells matured into oligodendrocytes and produced myelin around neurons.

Growing oligodendrocytes so that they myelinate neurons in a dish, similar to what happens in the brain, likely will lead to huge advances in the field.

It also will allow researchers to test how different molecules affect the different stages of myelination – experiments that could lead to the identification of compounds that repair myelin in demyelinating disease.

Barres’s lab is funded by the Myelin Repair Foundation (MRF), a private philanthropy using a novel business model to fund biomedical research. (See Foundation Tests Entrepreneurial Model for Medical Research.)

Source: Distinct Stages of Myelination Regulated by Gamma-secretase and Astrocytes in a Rapidly Myelinating CNS Coculture System by Trent A. Watkins, Ben Emery, Sara Mulinyawe, and Ben A. Barres, in the November 26 issue of Neuron.