LM11A-31 effective at improving limb movement after spinal cord injury in mice

Published on January 10, 2013 at 3:25 AM · 1 Comment

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 more than 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.

The experimental drug, called LM11A-31, was developed by study co-author Frank Longo, professor of neurology and neurological sciences at Stanford University. The drug is the first to be developed with a specific target, p75, as a potential therapy for spinal cord injury.

The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience.

Researchers gave three different oral doses of LM11A-31, as well as a placebo, to different groups of mice beginning four hours after injury and then twice daily for a 42-day experimental period. The scientists analyzed the compound's effectiveness at improving limb movement and preventing myelin loss.

The spinal cord injuries in mice mimicked those caused in humans by the application of extensive force and pressure, resulting in loss of hind-limb and bladder function and experimentally calibrated baseline difficulty in walking and swimming.

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Comments
  1. Prashant Sirisilla Prashant Sirisilla India says:

    What about those patients who got injured 5-7 years back and still not recovered. This drug can be used immediately after injury during the treatment or can be used for such patients too who is suffering of paralysis due to spinal cord injury. Plz reply..thank u.

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