Following a stroke, application of a drug that enhances neural plasticity during rehabilitation resulted in improved recovery of motor function, a new study in mice and monkeys reports. Furthermore, an early clinical trial evaluating the drug (for another condition) suggests the drug is safe in humans. After a stroke that results in brain damage, neurons can naturally "rewire" in the brain, an adaptation called plasticity, which allows individuals to recover some functions such as movement and speech. While the brain can be rewired to some extent through rehabilitation, there are no approved drugs that enhance brain plasticity and improve recovery. One protein that's known to play a role in plasticity and learning is CRMP2. Here, Hiroki Abe and colleagues studied how a small molecule that targets CRMP2, edonerpic maleate, might help boost recovery of motor functions following a stroke. They trained mice to complete a task where they must reach for food pellets, and then studied how well the mice could perform the task after a stroke, analyzing different combinations of administering edonerpic maleate, providing rehabilitation and/or administering a control substance that does not affect brain plasticity. Administering edonerpic maleate in combination with rehabilitation (but not the drug alone) significantly boosted the ability of the mice to perform the reaching task, the authors found. They performed similar experiments in monkeys trained in a reach-and-grab task; following stroke, monkeys given edonerpic maleate experienced quicker recovery of their motor function than controls, with the administration of edonerpic maleate being particularly helpful for restoring more demanding motor function during the later stages of rehabilitation. Simon Rumpel provides more context in a related Perspective.