Proliferation of NSCs and expression of Shh in Gli1-null mice.
An experimental drug GANT61 originally identified in a National Cancer Institute library of chemical compounds as a potential therapy for brain and basal cell cancers improves the symptoms of mice with a form of the debilitating neurological disorder multiple sclerosis (MS), according to new research.
It blocks the action of a key protein, Gli1, which is involved in so-called sonic hedgehog signaling, a biological pathway closely tied to neural stem cell development and the growth of some cancers, and whose signaling is raised in tissue samples taken from brain lesions in patients with MS.
In the study, mice with chemically damaged brain myelin were given daily doses of GANT61 for one month. Results showed that mice that received the drug had 50% more myelin at the end of treatment than did untreated mice. Also, GANT61-treated mice had an 8X increase in the number of neural stem cells that migrated to myelin-damaged areas of the brain and eventually developed into myelin-producing oligodendrocytes. Untreated mice did not show this increase.
Clinically, the researchers report, drug-treated mice were able to recover from an initial bout of MS-like paralysis and leg weakness. Untreated mice, however, endured repeated bouts of leg and bladder weakness, symptoms similar to those experienced by people with the disorder.
The study is the 1st to demonstrate neural stem cells, and not just early forms of oligodendrocytic cells, can be modified and recruited into myelin repair. Current treatments that target the immune system mostly slow the disease, which primarily targets myelin in the brain and spinal cord, but clinical experts have not yet been able to repair scarred and degraded myelin. It is also first to show that drugs targeted at sonic hedgehog, a pathway first discovered in the 1980s, can potentially treat neurological disorders, such as MS. “Our study results suggest that a potential long-term strategy for treating multiple sclerosis would involve treatments that separately target both neural stem cells, to help turn them into mature oligodendrocytes, as well as young and immature oligodendrocytes to produce more myelin,” says Salzer.
“Our findings also make clear that there is a resident population of adult neural stem cells that we can target and recruit to treat the disorder,” says Salzer. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14957.html http://www.newswise.com/articles/experimental-cancer-drug-shows-therapeutic-promise-in-mouse-models-of-multiple-sclerosis
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