Oral drug improves movement in mice with spinal cord injury

Washington, Jan ary 9: An experimental drug administered orally to mice after a spinal cord injury has proven effective when improving limb movement after an 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 and 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.”

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.

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.

Mice receiving the highest dose could walk with well-coordinated steps. In swimming tests, scientists saw similar improvements, with mice receiving the highest dose most able to coordinate hind-limb crisscross movement. The other treatment groups exhibited difficulty in walking and swimming.

The study was recently published in The Journal of Neuroscience. (ANI)