Researchers are edging closer to a therapy for Angelman syndrome that involves injecting molecules that can edit genes into the fetal brain. They have already succeeded in mice and say the approach could eventually treat people with the syndrome.
The work is of high interest because a similar strategy could also work for other genetic conditions linked to autism.
But the prospect of injecting molecules into fetal brains poses ethical questions, experts caution.
People with Angelman syndrome have severe developmental delays, seizures, impaired speech and, often, autism. They have a missing or mutated copy of a gene called UBE3A on the copy of chromosome 15 they inherit from their mother. The paternal copy is generally silent, so they have virtually no activity of the protein in neurons, where it is needed to modulate signals between neurons.
Other teams have tried to introduce a healthy copy of the gene or to unsilence the paternal copy in mice. But these strategies are ultimately impractical because they involve drugs with harsh side effects or giving children injections every few months.
In the new research, presented at a conference in February, Mark Zylka’s team injected the gene-editing enzyme CRISPR-CAS9 into the brains of embryonic mice. The method unsilenced the paternal copy of UBE3A in the mice. The researchers also rescued UBE3A expression in cultured human neurons, according to the unpublished findings.
Research suggests that the syndrome’s traits can be avoided if UBE3A is turned on before birth1. The work underscores the importance of intervening early in development.
“The earlier you put the genes back and try to fix the problem, the better the therapeutic benefit will be,” says Zylka, director of the Neuroscience Center at the University of North Carolina at Chapel Hill. “There’s a lot of interest in trying to break down this barrier to being able to treat prenatally.” The treatment may be tried in people within three to four years, Zylka says.
Experts caution that the work must be repeated in mice before it can be tested in people — and that scientists will first need to resolve the ethical concerns.
“Doing any gene manipulation in the fetal brain is kind of a dangerous thing to do, so that does concern me,” says Antonio Bedalov, associate member of the Fred Hutchinson Cancer Research Center in Seattle.
Scientists should move carefully because this is evolving research, others say.
“The idea that you could treat a fetus with [an enzyme] is just a very uncharted area, and there could contain a lot of risks,” says David Segal, professor of chemistry at the University of California, Davis, who was not involved in the research. “We need to move with caution.”
Full article: spectrumnews.org