Against traumatic encephalopathy
Gene therapy helped mice with "boxer dementia"
Sergey Kuznetsov, N+1
Scientists have developed a new way to combat chronic traumatic encephalopathy, a neurodegenerative disease that provokes permanent brain injuries. In an experiment on mice, they made their cells produce antibodies against tau, a protein that causes symptoms of CTE. The results of the study are published in the journal Human Gene Therapy (Sacramento et al., Anti-Phospho-Tau Gene Therapy for Chronic Traumatic Encephalopathy).
Chronic traumatic encephalopathy, which was originally called "boxer dementia" – a neurodegenerative disease caused by frequent head injuries, similar to Alzheimer's disease. Permanent head injuries provoke chronic inflammation, which in turn leads to the appearance of abnormal deposits of tau protein in neurons, astrocytes and around blood vessels throughout the brain, which leads to the death of its cells. Typical symptoms of chronic traumatic encephalopathy are depression, memory loss, dementia and suicidal behavior. Currently, there is no specific therapy aimed at CTE. Previously, scientists tried to treat the manifestations of this encephalopathy by injecting antibodies to tau protein into the body. Experiments on mice have yielded good results, but it hardly makes sense to use this technique on humans, since such an approach has shown very moderate results in the case of Alzheimer's disease. Experiments have shown that the blood-brain barrier passes no more than 0.5 percent of the injected antibodies into the brain.
Ronald Crystal from Vail Cornell Medical College in New York and his colleagues suggested that this problem can be solved by forcing the patient's body to independently produce antibodies against tau protein. To do this, it is necessary to introduce a gene that encodes antibodies into the central nervous system using viral vectors.
To test this hypothesis, the scientists conducted an experiment on transgenic mice of the C57BL/6 line at the age of 8-10 weeks. The animals were injected with painkillers, placed in a special fixing frame, where they received blows to the head – two blows a day with a six-hour interval for five days. After that, the condition of the mice was monitored during the day, and if they showed serious disorders – partial paralysis, apnea, other symptoms, they were excluded from the experiment.
Tau is a protein in the brain of a mouse from the control group (left) and in a mouse that received blows (here and below are pictures from an article in Human Gene Therapy).
The remaining mice (there were 38 of them), three weeks after the shock session, were injected directly into the hippocampus with a viral vector – the adenoassociated AAVrh.10 virus, which contained a sequence encoding antibodies from the tau protein. Another 10 mice who suffered strokes played the role of a control group, and they were not injected with viruses, and a group of 10 other mice received neither blows nor treatment. After a certain period of time – from six weeks to six months after therapy – the mice were killed, and the brain was examined using fluorescence microscopy. The results of the study showed that mice treated with viruses had significantly less tau protein in the brain than mice from the control group, or mice that received "empty" viruses without a genetic sequence encoding antibodies to tau protein.
Tau is a protein in the brains of mice receiving gene therapy (left), receiving "empty" viruses (in the middle), in the control group that did not receive therapy.
The authors of the study believe that this method will allow us to develop a new strategy designed to prevent the development of chronic traumatic encephalopathy in people who have suffered injuries.
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