Gene therapy could treat a rare brain disorder in the fetus | Science

Scientists are developing a radical form of gene therapy that could cure a devastating medical disorder by repairing mutations in the brain of fetuses in the womb.

The treatment, which has never been attempted before, would involve doctors injecting Feotus' brain with a harmless virus that infects neurons and delivers a series of molecules that correct genetic defects.

The tests suggest that the therapy will be more effective in the second trimester, when their brain will be in an early stage of development.

"We think this could be a treatment, if not a cure, depending on when it is injected," said Mark Zylka, a neurobiologist at the University of North Carolina.

The therapy targets a rare brain disorder called Angelman Syndrome, which affects one in 15,000 births. Children with this condition have a small brain and often have convulsions and have walking and sleeping problems. They can live all their life without saying a word.

According to Zylka, children with Angelman Syndrome may have such sleep difficulties that parents may feel that they must lock them in their room at night to prevent them from getting up and having accidents around the house.

Healthy people tend to have two copies of each gene in the genetic code, one inherited from their mother and the other from their father. But the two copies are not always enabled. For normal brain development, the mother copy of a gene called UBE3A is activated, while the father's copy is silenced.

In Angelman syndrome, the mother copy of UBE3A is missing or mutated, which means that no UBE3A is active. Zylka's therapy uses a version of a powerful gene editing tool called Crispr-Cas9 to restore the father's copy.

Studies in mice show that when gene therapy is administered in the uterus, it activates UBE3A in key parts of the brain. Speaking at a meeting of the American Association for the Advancement of Science in Washington, Zylka said the therapy activated the gene in the cortex, which is important for cognition , the hippocampus, essential for learning and memory, and the cerebellum, which controls movement.

Follow-up work has shown that it also works in human brain cells grown in a dish. "This really raises the possibility that this gene therapy can be used in humans," said Zylka.

Nobody has ever developed a gene therapy directly injected into the fetal brain. But Zylka thinks that if her work goes well, her therapy could be an important first that would pave the way for the treatment of other more common disorders, such as some forms of autism. "For many of these neurodevelopmental disorders, where the brain has developed inappropriately due to gene mutation, the best time to intervene is likely to occur early, very early," he said. .

Angelman's syndrome can be detected as early as 10 weeks after conception through a test to detect fetal DNA in the mother's blood. But there is no treatment available for women who are told that their baby has the disorder. "People get this diagnosis, and there is nothing to do, they have to make some pretty tough decisions at this point," Zylka said. "It can give them another option."