Human Stem Cells Cure Fatal Myelin Deficiency In Mice And Could One Day Help Children

Scientists in the US have used human cells that behave like stem cells to help "shiverer" mice grow myelin around their nerve fibres and thereby avoid an inevitable early death and poor quality of life; the researchers hope their finding will one day lead to treatments for similar neurological conditions in humans, and children especially.

The research is the work of neuroscientists at the University of Rochester Medical Center, New York, and is published in the June issue of the journal Cell Stem Cell.

The fattly myelin sheath that surrounds long fibre-like sections (axons) of nerve cells in the brain and spinal cord is like insulation around electrical wires - it stops leakage of electrical impulses that control vital body functions including movement. Insufficient or poorly working myelin causes a number of diseases, including a rare and fatal congenital disorder called pediatric leukodystrophy that affects thousands of children.

Like "shiverer" mice, so-called because they shake and wobble, children with pediatric leukodystrophy don't have enough myelin around their axons, and so the electrical impulses become weak and distorted, causing symptoms like difficulty standing and walking, seizures, dementia, paralysis, and eventually death. These are also the symptoms of other similar fatal, rare and equally uncurable childhood diseases such as Tay-Sachs, Krabbe's, Canavan's, Pelizaeus-Merzbacher, Vanishing White Matter Disease, and others.

Last week Lorenzo Odone, whose plight and courage, as well as the determination of his parents, was portrayed in the film Lorenzo's Oil, died from another such disease, adrenoleukodystrophy.

Myelin loss is also the reason for multiple sclerosis, and occurs to some extent in other diseases like diabetes and high blood pressure.

Study author and neurologist Dr Steven Goldman, is a leader in using stem cells to treat diseases of the nervous system. For this study, he and first author and scientist Dr Martha Windrem, who have been working on shiverer mice for over ten years, together with other colleagues, used a type of fetal human cell known as glial stem cells or glial progenitor cells. They are not quite like embryonic stem cells because they don't have the potential to become any type of cell in the body, they can only produce a limited range, including oligodendrocytes, the cells that make myelin.

The researchers injected the glial stem cells into 26 newborn shiverer mice that had been genetically programmed to have the condition, which normally results in early death about 20 weeks later, and a low quality of life characterized by seizures and other serious symptoms.

Most of the mice still died at the age typical for the disease, but six of them lived much longer, of which four appeared to be completely cured, something that has never been achieved before with shiverer mice.

Because of their experience with shiverer mice, Goldman, Windrem and colleagues knew how many human glial cells (around 300,000) to use in each mouse, and where to inject them in the mouse's brain (they chose five places) to ensure they migrated to all parts of the brain and spinal cord.

It took two months for the glial cells to multiply and spread, throughout the whole of the central nervous system, in the same way as they would in healthy mice. After that, they started to produce myelin, and continued for several months, coating all the axons in the entire brain and nervous system, until the cells were sending impulses correctly and just as quickly as in normal mice.

Four of the six mice survived one year after treatment, improved rapidly, had no seizures and were almost free of symptoms.

Goldman, who is Director of the Center for Translational Neuromedicine and professor of Neurosurgery and Neurology at Rochester, said:

"We kept expecting them to die. Not only did they not die, but they improved day by day."

Speculating as to why some mice lived longer and others died, Goldman said it was probably a race against time. For many of the mice, constant seizures killed them before the glial cells could settle and proliferate, they were too sick.

Goldman said he was very excited about the prospect of their findings leading not only to treatment but perhaps even a cure for the awful diseases that affect children.

But it will be some time before any treatments are developed and trialled, never mind be ready in time to help the thousands that are suffering today:

"Unfortunately, right now, we can do little more for many of these conditions besides tell parents to prepare for their kids to die," said Goldman.

"Neonatal Chimerization with Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise Lethally Hypomyelinated Shiverer Mouse."
Martha S. Windrem, Steven J. Schanz, Min Guo, Guo-Feng Tian, Vaughn Washco, Nancy Stanwood, Matthew Rasband, Neeta S. Roy, Maiken Nedergaard, Leif A. Havton, Su Wang, and Steven A. Goldman.
Cell Stem Cell, Vol 2, 553-565, 05 June 2008.