Public release date: 8-Jan-2013 [ | E-mail | Share ]
Contact: Sung Ok Yoon Sung.Yoon@osumc.edu 614-292-8542 Ohio State University
COLUMBUS, Ohio An experimental oral drug given to mice after a spinal cord injury was effective at improving limb movement after the injury, a new study shows.
The compound efficiently crossed the blood-brain barrier, did not increase pain and showed no toxic effects to the animals.
"This is a first to have a drug that can be taken orally to produce functional improvement with no toxicity in a rodent model," said Sung Ok Yoon, associate professor of molecular & cellular biochemistry at Ohio State University and lead author of the study. "So far, in the spinal cord injury field with rodent models, effective treatments have included more than one therapy, often involving invasive means. Here, with a single agent, we were able to obtain functional improvement."
The small molecule in this study was tested for its ability to prevent the death of cells called oligodendrocytes. These cells surround and protect axons, long projections of a nerve cell, by wrapping them in myelin. In addition to functioning as axon insulation, myelin allows for the rapid transmission of signals between nerve cells.
The drug preserved oligodendrocytes by inhibiting the activation of a protein called p75. Yoon's lab previously discovered that p75 is linked to the death of these specialized cells after a spinal cord injury. When they die, axons that are supported by them degenerate.
"Because we know that oligodendrocytes continue to die for a long period of time after an injury, we took the approach that if we could put a brake on that cell death, we could prevent continued degeneration of axons," she said. "Many researchers in the field are focusing on regeneration of neurons, but we specifically targeted a different type of cells because it allows a relatively long therapeutic window."
An additional benefit of targeting oligodendrocytes is that it can amplify the therapeutic effect because a single oligodendrocyte myelinates multiple axons.
A current acute treatment for humans, methylprednisolone, must be administered within eight but not after 24 hours after the injury to be effective at all. An estimated 1.3 million people in the United States are living with spinal cord injuries, experiencing paralysis and complications that include bladder, bowel and sexual dysfunction and chronic pain.
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First oral drug for spinal cord injury improves movement in mice, study shows
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