Against stroke and AIDS
Mutation of one gene can help to recover after a stroke
Lina Medvedeva, XX2 century
Even as a result of a mild stroke, the patient may be left with a weakened leg or arm, poor muscle control, memory lapses, besides, all these symptoms increase with age. Neuroscientists from the University of California at Los Angeles (University of California, Los Angeles) in collaboration with colleagues from Israel found that patients with a congenital mutation of the CCR5 gene recovered better in the case of a mild stroke than patients with a complete copy of this gene.
Article by Joy et al. CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury published in the journal Cell.
"For the first time, a human gene has been linked to signs of recovery from stroke," says Dr. Thomas Carmichael, one of the authors of the study. "Our research opens up an opportunity to improve the health of patients and their quality of life."
(The press release of A missing gene makes a big difference in patients’ recovery from mild stroke is published on the UCLA – VM website.)
CCR5 performs various functions in our body. In particular, in lymphocytes, the protein encoded in it is a receptor that HIV uses to penetrate into the cell. A small part of the human population has a mutation in this gene (deletion of 32 nucleotides, CCR5Δ32), which blocks the interaction of the virus with the receptor and makes its carrier resistant to infection. This is the same gene that the world-famous He Jiankui modified using the CRISPR method to obtain human embryos immune to HIV.
The work of researchers from California is based on a previous study conducted on mice at the same university. In the absence of CCR5, the mice improved their ability to form new neural connections and restore the brain after damage.
Due to the fact that maraviroc blocks CCR5, Carmichael and his colleagues made the assumption that the drug can also speed up recovery after a stroke. His laboratory, in collaboration with pharmacologist Esther Shohami from the Hebrew University in Jerusalem, tested the effectiveness of the drug in suppressing CCR5 in a mouse model.
"We found out that maraviroc blocked CCR5 in mice and triggered the recovery of animals after traumatic brain disease and stroke," says Carmichael. "It remained questionable whether CCR5 suppression would give the same results in humans."
Knowing that deletion in the CCR5 gene occurs in Ashkenazi Jews, Carmichael and his colleagues turned to researchers from Tel Aviv University. By a happy coincidence, Israeli scientists have already observed 446 stroke patients in a non-experimental study.
The study by neuroscientist Einor Ben Assayag focused only on patients who had mild and moderate strokes. Her colleagues recorded improvements in patients' walking, hand and foot control, and other types of movement.
"There were blood samples from patients in the Einor laboratory, and scientists assessed their recovery from stroke at intervals of six months, a year and two years," says Carmichael. "People with a non-functional copy of the CCR5 gene showed significantly better signs of recovery of motor skills, language and sensory functions." A year after the stroke, such patients also showed the best results of tests evaluating memory, verbal functions and attention.
Neurons produce a protein encoded by the CCR5 gene only during or after a stroke. Removing CCR5 seems to be able to improve recovery by increasing plasticity – the ability of the brain to recover after a lesion.
The next step for scientists is to launch clinical trials of the effectiveness of the drug maraviroc on stroke patients who have the CCR5 gene.
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