For decades, the only viable tool to help stroke patients regain lost motor abilities — like walking or moving an arm — has been grueling physical rehabilitation. But what if a pill could do the work of months of therapy?
A team of researchers at UCLA Health has taken a significant step toward that future. They report the discovery of a drug that fully replicates the effects of physical rehabilitation in mice recovering from stroke. The findings could one day transform how we treat stroke, the leading cause of adult disability worldwide.
One Step Closer to a Drug That Replicates Stroke Rehabilitation
Every year, nearly 800,000 people in the United States suffer a stroke. For many, the aftermath is life-altering. Simple tasks like picking up a cup or walking across a room become monumental challenges. Rehabilitation can help, but its effects are often limited.
When a stroke strikes, it cuts off blood flow to part of the brain, killing neurons and disrupting the neural networks that control movement. Rehabilitation works because it encourages the brain to form new connections, but how this happens at the cellular level has long been a mystery.
The new study focused on a specific group of neurons in the motor cortex, the brain region responsible for movement. Using a mouse model of stroke, the team discovered that rehabilitation after a stroke selectively strengthens connections between a specific type of brain cell, known as parvalbumin interneurons, and a group of neurons that project to the damaged area.
After a stroke, gamma oscillations disappear, and parvalbumin neurons lose their connections. Gamma oscillations are like the beat of a drum, keeping the brain’s neurons in sync. When these rhythms are disrupted, movement becomes uncoordinated. Rehabilitation, the researchers found, restores these oscillations and repairs the neural networks.
The researchers led by Dr. Thomas Carmichael, the chair of UCLA Neurology, tested two compounds designed to excite parvalbumin neurons and reignite gamma oscillations. One of the drugs, DDL-920, stood out. In mice, it not only restored gamma oscillations but also led to significant improvements in movement control.
“The goal is to have a medicine that stroke patients can take that produces the effects of rehabilitation,” said Carmichael. “Rehabilitation after stroke is limited in its actual effects because most patients cannot sustain the rehab intensity needed for stroke recovery.”
Real Progress
‘Oh, great! Another study on mice,’ some of you might quip. But there is real cause for optimism. The researchers also studied stroke patients and found that those who recovered better had stronger gamma oscillations in their brains. This suggests that the same mechanisms may be at work in humans.
“Gamma oscillations increase in stroke patients during rehabilitation recovery after stroke, as they do in the mouse,” the researchers wrote. This opens the door to new treatments that could enhance these brain rhythms, potentially speeding up recovery.
The study also highlights the importance of timing. Rehabilitation, the scientists found, is most effective in the weeks and months following a stroke, when the brain is most plastic. By targeting parvalbumin interneurons during this critical period, doctors might be able to maximize recovery.
While the results are promising, the drug is far from ready for human use. “Further studies are needed to understand the safety and efficacy of this drug before it could be considered for human trials,” Carmichael cautioned.
Stroke recovery has long been a neglected area of medicine. Unlike heart disease or cancer, there are no drugs to treat the lingering effects of stroke.
“Stroke recovery is not like most other fields of medicine, where drugs are available that treat the disease,” Carmichael said. “We need to move rehabilitation into an era of molecular medicine.”
The findings appeared in the journal Nature Communications.
