研究工作由纽约罗彻斯特大学医学中心的神经科学家完成，并发表于六月号《细胞—干细胞》（Cell Stem Cell）杂志上。
关于“震颤鼠” 名称的来历，是因为这种实验鼠摇摇晃晃、浑身发抖；患有小儿脑白质营养不良的孩子就象“震颤鼠”，没有足够的髓磷脂环绕轴突，因此电脉冲变弱且扭曲变形，导致诸如站立与行走困难、惊厥、痴呆与瘫痪等症状并最终死亡。同时也存在其它致命、罕见、同样无法治愈的儿科疾病，如家族黑蒙性痴呆（Tay-Sachs Disease）， 球样细胞脑白质营养不良（克腊比氏病, Krabbe's Disease ），康纳丸氏病（Canavan’s Disease），佩-梅病（Pelizaeus-Merzbacher Disease）, 白质消融性白质脑病（Vanishing White Matter Disease） 及其它等等。
罗伦佐•奥登（Lorenzo Odone），其境其情及其父母的勇毅果决曾被搬上了银幕－电影《罗伦佐的油》（Lorenzo's Oil）， 在上个星期死于另外一种此类疾病：脑白质营养不良。
该研究报告的作者与神经学家史蒂芬•戈德曼（Steven Goldman）博士，在干细胞治疗神经系统疾病领域处于领先地位。为进行这项研究，他与第一作者、科学家马太•温德里姆（Martha Windrem）博士（他十余年来一直在研究“震颤鼠”）与其他同事一道，用众所周知的神经胶质干细胞或神经胶质祖细胞中的一种作实验。这种干细胞与胚胎干细胞并非非常相似，因为其并未有潜力发育成为身体中的任何类型细胞，而只能产生范围有限的、可产生髓磷脂的包括少突细胞在内的细胞。
Human Stem Cells Cure Fatal Myelin Deficiency In Mice And Could One Day Help Children
Main Category: Stem Cell Research
Also Included In: Pediatrics / Children's Health; Multiple Sclerosis; Neurology / Neuroscience
Article Date: 05 Jun 2008 - 12:00 PDT
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.