A University of Virginia School of Medicine scientist is developing an innovative gene therapy she hopes will slow disease progression and improve movement, coordination and communication in children with Rett syndrome. The approach also may be useful for battling other genetic disorders involving the X chromosome.
UVA researcher Sanchita Bhatnagar discovered that tiny bits of RNA, called microRNAs, play an important role in Rett, a rare genetic disorder that can impair children’s ability to speak, move and even breathe. Based on that finding, she is seeking to sop up those RNA bits, called microRNA, using absorbent particles called microRNA sponges.
Early work in lab models has produced promising results, and she hopes the approach could lead to a better quality of life for children with Rett.
“We are seeing that lab animals treated with this gene therapy are more mobile. They’re moving faster, they’re smarter,” Bhatnagar said. And if that translates into even modest improvements for children, it could make a big difference, she said: “If we can help a child to move more independently, or improve their ability to communicate, I think for a parent, that’s a big win.”
About Rett Syndrome
Rett syndrome affects approximately 1 in 10,000 children, almost exclusively girls. That’s because it’s caused by a mutation in the MECP2 gene found on the X chromosome. Girls have two X chromosomes, while boys have an X and a Y.
Bhatnagar’s discovery of the role of microRNA in Rett came as a surprise, because it was the first time microRNA had been linked to X chromosome biology. That finding dovetailed perfectly with her lab’s expertise in creating microRNA sponges that can target microRNA, absorbing it and then breaking it down.
“We are not altering the genomic DNA,” Bhatnagar emphasized. “We are just using them [the microRNA sponges] as inhibitors that are delivered through [adeno-associated viral] vectors. These vectors do not go and integrate into the genome, so we hope for minimal secondary effects.”