Hints have been accumulating that maraviroc, a drug for slowing HIV, could benefit patients who have suffered mild stroke. A few years ago, maraviroc was shown to improve learning and memory in mice. And a new study, also in mice, indicates that the drug enhances motor recovery after stroke and improves cognitive function after traumatic brain injury. The new study also presents information from a unique patient population to strengthen the case that maraviroc could lessen stroke’s harms in people.
The people evaluated in the current study carry a mutated version of the CCR5 gene, which expresses a cell receptor protein that can be blocked by maraviroc. When CCR5 is expressed on human immune cells, it can serve as an entry point for HIV. CCR5, it happens, can also be expressed in cortical neurons, but only during or after stroke.
Carriers of mutated CCR5, the new study indicates, have better outcomes after stroke. Details appeared February 21 in the journal Cell, in an article titled, “CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury.” The fruit of a collaboration between scientists based at UCLA and Hebrew University, the article speculates that inhibiting the expression of CCR5 promotes recovery by enhancing plasticity, the ability of the brain to rewire itself after injury.
“Recovery is associated with preservation of dendritic spines, new patterns of cortical projections to contralateral pre-motor cortex, and upregulation of CREB and DLK signaling,” the article’s authors wrote. “Administration of a clinically utilized FDA-approved CCR5 antagonist, devised for HIV treatment, produces similar effects on motor recovery post stroke and cognitive decline post-traumatic brain injury.”
When the UCLA team, led by S. Thomas Carmichael, MD, PhD, chair and professor of neurology, decided to evaluate whether targeting CCR5 with maraviroc could accelerate recovery from stroke, it teamed with pharmacologist Esther Shohami, PhD, at Hebrew University to test the drug’s effectiveness in suppressing CCR5 in a mouse model.
“We found that maraviroc blocked CCR5 in mice and boosted the animals’ recovery from traumatic brain injury and stroke,” said Carmichael. “The big question left to answer was whether eliminating CCR5 would produce the same results in people.”
Knowing that CCR5 deletion is common in Ashkenazi Jews, Carmichael and his team reached out to researchers at Tel Aviv University. In a lucky coincidence, the Israeli scientists were already following 446 stroke patients in an observational study.
Led by neuroscientist Einor Ben Assayag, PhD, the study focused only on patients who had suffered mild or moderate strokes. Her team documented the patients’ improvements in walking, arm and leg control, and other types of movement.
“Einor’s lab had the patients’ blood samples and was evaluating their recovery from stroke after intervals of six months, one year, and two years,” said Carmichael. “People missing the CCR5 gene showed significantly greater recovery in motor skills, language, and sensory function.”
One year after stroke, patients missing CCR5 also scored higher in tests assessing memory, verbal function, and attention.
“When you suffer a stroke, part of your brain dies, severing those cells’ connections with neurons in other regions. That’s why stroke patients often suffer paralysis or lose speech,” Carmichael said. “When CCR5 is missing or blocked, neurons can make new connections and rewire the brain, enabling patients to regain some lost function.”
The scientists’ next step will be to launch a clinical trial testing the effectiveness of the drug maraviroc on stroke patients with the CCR5 gene.
