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Gene in Infamous Experiment on Embryos Points to New Stroke Treatment



A widely criticized experiment last year saw a researcher in China delete a gene in twin girls at the embryonic stage in an attempt to protect them from HIV. A new study suggests that using a drug to remove the same gene in people with stroke or traumatic brain injuries could help improve their recovery

The new work shows the benefits of turning off the gene in stroke-induced mice by using the drug , already approved as an HIV treatment. It also focuses on a sample of people who were naturally born without the gene. People without the gene recover faster and more completely from stroke than the general population does, the researchers found. boost recovery in humans after a stroke or traumatic brain injury, says S. Thomas Carmichael, the study's senior researcher and neurologist at the University of California, Los Angeles, David Geffen School of Medicine.

The combination of mouse research and leveraging human genetic data to confirm the relevance of drug targets makes the new research a "landmark paper," says Jin- Moo Lee, co-director of the Barnes-Jewish Hospital and the Washington University Stroke and Cerebrovascular Center in Saint Louis who was not involved with the work

At the end of 201

8 He Jiankui, then at the Southern University of Science and Technology in China , said he had edited the CCR5 genes of twin girls at the embryonic stage in an effort to protect them against HIV infection.

Carmichael and others have spent years looking for genes and other biological pathways that could lead to medications to help the child. brain repair itself after a stroke or brain injury. CCR5 is the first such candidate to show real promise, some experts say. For stroke and traumatic brain injury patients, "I believe this is the beginning of hope," says Alcino Silva, and neuroscientist at U.C.L.A. who worked with Carmichael on the new study. of HIV and AIDS. Carmichael gave the drug, called maraviroc, to stroke-induced mice. Knocking down the gene's activity in the brain's motor neurons has a tremendous effect on recovery, "he says. "The drug does not easily cross the blood-brain barrier, but it is enough to preserve brain connections involved in chemical signaling and to increase connectivity between brain regions," the study showed.

For the human-validation component study, the team examined 68 individuals without CCR5 genes, along with 446 controls. Those who suffered strokes-and also had the natural gene deletion-recovered movement abilities faster and had fewer cognitive deficits months after stroke than those who had intact CCR5 . The exact mechanism behind the result is unknown. In healthy people the CCR5 gene is thought to promote learning and memory by acting as a "stop" signal, telling neurons to receive only one memory and hold it, rather than continuing to receive and retain any signal that comes in, Carmichael says. Immediately after a stroke or brain injury the gene helps tamp down the excitability of neurons, helping to limit damage, he says. But if the gene keeps pumping out "stop" signals, it also interferes with the brain's ability to build new connections and repair damage, he adds.

Carmichael's approach is to turn off these signals by starting people on the drug about five to seven days after a stroke and continuing for about three months, allowing the brain to get better chance to recover. In the current clinical trial, participants also undergo intensive physical therapy to restore movement. This two-pronged approach to treatment is important, says Steven Cramer, and stroke recovery expert at the University of California, Irvine, who did not take part in the research. Drug therapy can open the door to reshaping brain circuits, but recovery also requires individual effort – just like learning the task in the first place – he notes. "Just because you sprinkle the magic pixie dust on the brain, does not mean you fix the problem," he says. "

Cramer says he thinks treatment with anti- CCR5 drugs could become" one of the major pillars "of therapeutic advances in stroke recovery


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