A new study found that an HIV drug, as well as a genetic mutation linked to HIV resistance, can improve recovery from stroke or traumatic brain injury.
Published in the journal Cell, the study had two prongs: The first, in mice, found that the HIV entry inhibitor maraviroc enhances recovery of motor skills after strokes and improves cognitive function after traumatic brain injury. The second prong, which looked at people who’d had a stroke who also have a the CCR5 mutation known as Delta32, found they experience greater recovery of neurological impairments and cognitive function after neurological events even without medication like maraviroc.
The Delta32 mutation has made headlines recently after an HIV-positive man who received a bone marrow stem cell transplant from a donor with Delta32 went into HIV-remission. The mutation prevents a protein called CCR5 from rising to the surface of T cells, where HIV can attach to it and invade cells.
Maraviroc also uses CCR5 to prevent HIV from infecting more T cells, and it is prescribed in conjunction with other antiretrovirals. Maraviroc covers the CCR5, where HIV would normally grab on, thus preventing the virus from attaching.
But how does something that fights HIV also help in recovery after stroke or traumatic brain injury?
It turns out CCR5 is also expressed in cortical neurons, but only during or after a stroke. Researchers believe that blocking CCR5 helps speed recovery by enhancing what’s known as plasticity, the brain’s ability to rewire itself after injury. Repairing or rerouting neural pathways allows people to recover cognitive and motor skills that may have been lost due to damage to the brain (whether caused by a blood clot as in a stroke, or a traumatic brain injury).
“When you suffer a stroke, part of your brain dies, severing those cells’ connections with neurons in other regions,” said senior author, Dr. S. Thomas Carmichael, chair of the neurology department at the David Geffen School of Medicine at UCLA, to Genetic Engineering and Biotechnology News. “That’s why stroke patients often suffer paralysis or lose speech. When CCR5 is missing or blocked, neurons can make new connections and rewire the brain, enabling patients to regain some lost function.”
Previous research indicates that the Delta32 mutation may be most common among those whose ancestors survived the devastating bubonic plague outbreaks in Europe between mid-1300s and 1750. That mutation appears to render people immune to HIV and — according to these findings — more likely to recover from a stroke.
This study was a collaboration between several research schools. A team at University of California Los Angeles led by Carmichael, set out to evaluate whether targeting CCR5 with maraviroc could speed up post-stroke recovery. They enlisted pharmacologist Esther Shohami, at Hebrew University, to test maraviroc’s effectiveness in suppressing CCR5 in mice. The results were positive.
“We found that maraviroc blocked CCR5 in mice and boosted the animals’ recovery from traumatic brain injury and stroke,” Carmichael reported. “The big question left to answer was whether eliminating CCR5 would produce the same results in people.”
Aware that the CCR5 mutation is common among Ashkenazi Jews, Carmichael’s team contacted Tel Aviv University in Israel, where neuroscientist Einor Ben Assayag, was already evaluating the recovery of people who had suffered mild or moderate strokes.
“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, adding that those with the Delta32 mutation “showed significantly greater recovery in motor skills, language, and sensory function.”
Fortunately, in maraviroc (Selzentry), scientists already have a drug that can mimic the impact of Delta32. Next, researchers plan to put the drug through clinical trials. Having been previously proven safe for humans gives maraviroc a head start toward Food and Drug Administration approval.