Human Stem Cells Show Promise Against Fatal Children's Diseases
ScienceDaily (Jun. 4, 2008) - Scientists have used human stem cells to 
dramatically improve the condition of mice with a neurological condition 
similar to a set of diseases in children that are invariably fatal, 
according to an article in the June issue of the journal Cell Stem Cell.
With a one-time injection of stem cells just after birth, scientists were 
able to repair defective wiring throughout the brain and spinal cord -- the 
entire central nervous system -- of mutant "shiverer mice," so called 
because of the way they shake and wobble. The work marks an important step 
toward the day when stem cells become an option for the treatment of 
neurological diseases in people.
Neuroscientists at the University of Rochester Medical Center injected a 
type of fetal human stem cell known as glial stem cells into newborn mice 
born with a condition that normally claims their lives within about 20 weeks 
of birth, after a lifetime of seizures and other serious consequences. While 
most of the 26 mice that received transplanted glial stem cells still died, 
a group of six lived far beyond their usual lifespan, and four appeared to 
be completely cured -- a first for shiverer mice. The scientists plan to 
gather more evidence before trying the approach in sick children.
"It's extremely exciting to think about not only treating but actually 
curing a disease, particularly an awful disease that affects children," said 
neurologist Steven Goldman, M.D., Ph.D., a leader in manipulating stem cells 
to treat diseases of the nervous system. "Unfortunately, right now, we can 
do little more for many of these conditions besides tell parents to prepare 
for their kids to die."
Thousands of children with rare, fatal disorders known as pediatric 
leukodystrophies share a central problem with the shiverer mice: Their brain 
cells lack sufficient myelin, a vital fatty coating that wraps around cells 
in the brain like insulation around an electrical wire. Myelin coats long 
sections, known as axons, of brain cells called neurons, and without it, the 
electrical signaling between neurons becomes sluggish and muddied, causing a 
variety of symptoms. Myelin loss is at the heart of multiple sclerosis, and 
also plays a role in the symptoms of diabetes, high blood pressure, and 
other diseases.
In children, diseases of myelin go by a host of names but share the same 
features: a childhood and young adulthood that may include weakness, 
difficulty standing or walking, seizures, dementia, paralysis, and 
ultimately, death. These diseases, which include Tay-Sachs, Krabbe's, 
Canavan's, Pelizaeus-Merzbacher, Vanishing White Matter Disease and a host 
of others are each rare, but collectively they kill thousands of children 
every year. Just last week, Lorenzo Odone, whose battle with one such 
disease, adrenoleukodystrophy, was featured in the film Lorenzo's Oil, 
passed away. Currently there is no treatment for any of these conditions.
Goldman and first author and scientist Martha Windrem have been working on 
shiverer mice for more than a decade. In work published in 2004 in Nature 
Medicine, the team restored myelin in a widespread area of an animal's 
brain, by injecting human stem cells that eventually become 
oligodendrocytes, the cells that produce myelin. In those earlier 
experiments, the team attempted to repair cells in only certain parts of the 
brain. Although the methods were effective, the treatment didn't actually 
improve the health of the mice.
In the latest work, the team took advantage of the routes that cells 
commonly take to migrate from one region of the brain to another. They 
injected approximately 300,000 human stem cells into the brain of each 
mouse, choosing five particular spots because of their ability to serve as 
launch pads of sorts for stem cells to migrate and colonize the entire brain 
and spinal cord.
And that's just what happened in some of the mice. In just two months, the 
glial stem cells multiplied and spread, covering nerve cells in almost the 
entire central nervous system, exactly mirroring their distribution in the 
brains of healthy mice. For several months after that, the cells produced 
myelin that coated nerve cells throughout the entire brain and spinal cord; 
from then on, the brain cells functioned normally, conducting impulses as 
quickly as in normal mice.
Not all of the transplanted mice fared well. Of 26 mice treated with stem 
cells, about three-quarters died, typically from seizures, within a couple 
of weeks of their untreated counterparts. But the six treated mice that 
lived longer recuperated to a degree hardly thought possible. The four mice 
that still survived one year after treatment improved rapidly, had no 
seizures, and were practically free of symptoms.
"We kept expecting them to die. Not only did they not die, but they improved 
day by day," said Goldman, who is director of the Center for Translational 
Neuromedicine and professor of Neurosurgery and Neurology.
The stem cells established themselves and spread throughout the brain with 
similar success in all the transplanted mice, including the ones that died 
near the time of their untreated counterparts. So why did some mice live 
longer? Goldman believes it was a race against time: Many of the mice were 
so sick that constant seizures killed them before the stem cells could take 
hold, propagate, spread, and remyelinate brain cells.
The work was made possible thanks to funding from the Adelson Medical 
Research Foundation, the Mathers Charitable Foundation, and the National 
Multiple Sclerosis Society.
In addition to Windrem and Goldman, other Rochester authors of the paper 
include Steve Schanz; Min Guo, Ph.D.; Vaughn Washco; Su Wang, Ph.D.; 
Guo-Feng Tian, Ph.D.; Maiken Nedergaard, M.D., Ph.D.; and Nancy Stanwood, 
M.D. Other authors include Matthew Rasband of the Baylor College of 
Medicine, Neeta Roy of Weill Cornell Medical Center, and Leif Havton of 
UCLA.

Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
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