06 June 2008

Stem cells against neurodegenerative diseases: one more step

Alexey Levin, Voice of AmericaAnimal experiments have been carried out at the University of Rochester (New York State), which prove the fundamental possibility of using stem cells to combat an extensive family of incurable diseases developing in children with disorders of the normal formation of protective membranes covering nerve fibers.

The shells work like insulation of electrical wires, preventing leakage of electrical impulses passing through the nerves. They consist of myelin, a specific white substance that includes protein and fat–like components.

There is an extensive group of diseases that lead to damage or destruction of myelin sheaths in adults (this process is called demyelination). The most famous of them is multiple sclerosis, but there are many others.

With children, the situation is different. In newborn infants, many nerve fibers do not yet have fully formed myelin covers, and this is quite normal. Pathologies occur when the covers remain unfinished. Such diseases are called leukodystrophy – more precisely, pediatric leukodystrophy. They have many specific names: Gaucher disease, Canavan disease, Crabbe disease, Niemann-Pick disease, Tay-Sachs disease. There are also rare genetic diseases in which demyelination does not begin after reaching adulthood, but in childhood or adolescence – these are adrenoleukodystrophy and adrenomyeloneuropathy.

Steven Goldman, professor of neurosurgery and neurology at the University of Rochester, and members of his group worked with mice whose normal myelin synthesis was disrupted as a result of the mutation. There is a pure laboratory line of such mice, which are usually called shakers, because they suffer from seizures and can only make sharp and uncoordinated movements. The experimenters crossed mice of this line with other genetically engineered mice with severely weakened immune systems. As a result, they got shaking mice with suppressed immunity, which could be injected with foreign biomaterials without fear of their rejection.

The researchers selected 26 such newborn mice and injected them with 300 thousand human stem cells, from which cells of the neuroglia, the supporting tissue of the central nervous system, are born. They hoped that this procedure would trigger the process of myelination of nerve fibers and thereby allow the animals to find a normal existence. These hopes were fulfilled – but only partially. Twenty-two mice died within five months, which is always the case with shaking mice. However, there were also four lucky people who lived for over a year. During the first four months after birth, they showed the same pathological symptoms as their less fortunate relatives, but then their condition began to gradually improve. The mice stopped having seizures and started moving almost normally.

When the animals were 14 months old, the experimenters killed them to conduct a microscopic examination of brain tissue. As expected, the nerve fibers in the stem cell insertion zones were coated with myelin. (The green image from the University of Rochester website shows the neurons on which the myelin coating has been restored). The results of the experiments are summarized in an article published on June 5 by the journal Cell Stem Cell.

Scientists admit that the percentage of cure is still small. However, they believe that there are ways to increase it. The results of the experiments indicate that the injected stem cells trigger the synthesis of myelin rather slowly – after all, the condition of both the surviving and dead mice worsened at first. Steven Goldman hopes to find anticonvulsant medications that will allow mice to live up to 4-5 months, and thus give stem cells time to continue working on the formation of myelin sheaths.  Most likely, these experiments will take several more years. If they lead to success, it will be possible to think about clinical trials of this method.

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