In the United States, strokes are a leading cause of disabilities, with more than six million Americans suffering from arm and leg weakness, poor muscular control, and memory lapses (amongst other symptoms) after even mild instances. This past week, UCLA scientists discovered a key link between a particular gene (known as CCR5) and recovery from strokes — namely, the fact that those patients who lacked CCR5 had an improved course of recovery from mild stroke than patients with the gene.
According to senior author Dr. S. Thomas Carmichael, chair of the neurology department at the David Geffen School of Medicine at UCLA, such a revelation may be a deciding factor in the formation of the first pill to counteract the physical and mental aftermath of mild stroke.
The CCR5 gene plays a plethora of roles as a member of the beta chemokine receptor family, a seven transmembrane protein similar to G Protein coupled receptors (GPCRs). Expressed by T cells and macrophages, this protein is known to be a co-receptor for macrophage tropic viruses such as HIV to enter host cells. Current data built upon from prior research suggests that suppressing CCR5 enhances neurons' ability to form new connections and rewire the brain after injury. A study performed in 2016 by UCLA neurobiologist Alcino Silva demonstrated that maraviroc, an FDA-approved drug that targets CCR5 in order to reduce the spread of HIV in patients, improved learning and memory in mice.
From this data, Carmichael hypothesized that maraviroc could also accelerate patients' rate of recovery from stroke. His team partnered with pharmacologist Esther Shohami at Hebrew University to test the drug's effectiveness in a mouse model, and concluded that maraviroc blocked CCR5 in mice and boosted their recovery from traumatic brain injury and stroke.
Armed with the knowledge that CCR5 deletion is a common genetic trait of Ashkenazi Jews, Carmichael and his team reached out to Tel Aviv University scientists (led by neuroscientist Einor Ben Assayag) who were following stroke patients in an observational study, documenting their improvements in movement following their incidents. Patients missing the CCR5 gene were found to have significantly greater recovery in motor skills, language, and sensory function. Approximately one year after stroke, these same patients also scored higher in tests assessing memory, verbal function and attention, as compared to patients expressing the CCR5 gene. The CCR5 deletion appears to enhance recovery by enabling plasticity, allowing neurons to make new connections to rewire the brain, and regain lost function.
The scientists' next steps will include launching of clinical trials testing the effectiveness of maraviroc on stroke patients with the CCR5 gene. While there is still a ways to go in terms of complete recuperation, these promising developments will surely be instrumental in the development of drugs and medical techniques designed to accelerate recovery from stroke through gene silencing.