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Neuroscience

Small molecule speeds up recovery after brain damage in animals

Combined with rehabilitation, compound may help stroke patients regain lost motor function, researchers say

by Tien Nguyen
April 9, 2018 | A version of this story appeared in Volume 96, Issue 15

Structure of edonerpic maleate.

In the minutes after a stroke, the sudden loss of blood supply to a region of a person’s brain can start damaging brain cells. Acute therapies to restore blood flow can protect neurons near the damaged cells, if the person receives treatment in the hours after the stroke. But once that window closes, doctors have few therapeutic options.

Damaged neurons can impair stroke patients’ cognitive abilities and motor skills. However, with rehabilitation, affected people can recover some lost function thanks to the brain’s ability to rewire its circuitry—known as synaptic plasticity.

Now, scientists at Yokohama City University and Fujifilm’s Toyama Chemical report that the small molecule edonerpic maleate, when administered in combination with physical training, accelerates the recovery of lost motor function caused by a brain injury in mice and monkeys (Science 2018, DOI: 10.1126/science.aao2300).

Toyama had previously sponsored Phase I/II clinical trials of edonerpic maleate for treating Alzheimer’s disease. The trials demonstrated that the molecule was safe but not efficacious. But because the compound protected neurons in preclinical studies, the research team behind the new work decided to test the molecule’s ability to recover function after stroke-like brain injuries.

The team tested the compound in two-month-old male mice and five-year-old macaque monkeys that had received brain injuries. The scientists tested the animals’ motor skills before and after the injury. Those receiving rehabiliative training and oral doses of edonerpic maleate starting one day after injury recovered more motor function after the injury than those that didn’t receive both.

Louise D. McCullough, who studies stroke at the University of Texas Health Science Center, says the findings are provocative but need to be validated. Translating the results to people may be somewhat limited because the team tested only young, male animals. Many researchers have reported sex and age differences in the response to brain injuries, she says.

The authors plan to evaluate edonerpic maleate in a 40-person Phase II clinical trial slated to start by early 2019.

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