The reactivation of the silent genes offers hope for the treatment of Rett syndrome

Scientists led by UC Davis Health Scientist Sanchita Bhatnagar have developed a promising gene therapy that can treat Rett. The therapy works on reactivating healthy but quiet genes responsible for this rare disorder and perhaps other combined conditions X, such as a delicate syndrome X.

Their findings were published in.

About the Rett team

The Rett syndrome is a genetic state that mainly affects girls. This is due to the defective MECP2 gene on the X chromosome. This gene contains the Synthesis instructions for the MECP2 protein synthesis.

Girls with a retta syndrome may have too much protein or their protein may not work properly. Protein deficiency can cause a number of symptoms, including speech loss, handicapped hand movements, breathing difficulties and attacks.

Muted genes

Women have two X chromosomes (xx). In each cell, one X chromosome will be randomly muted in a process known as inactivating X (XCI) chromosome. In girls with a retta syndrome, the calm chromosome has a healthy copy of MECP2.

Our study concerned the reactivation of a muted X chromosome carrying a healthy gene.

Sanchita Bhatnagar, senior author of Study

Bhatnagar is an associate professor in the Department of Medical Microbiology and Immunology UC Davis and runs the Bhatnagar Laboratory. She is an assistant to the leader of the research program at the UC Davis Comprehensive Cancer Center and researcher at the Mind Institute.

Sponge -like molecules to overcome the power of silence micro

The new study was carried out by research in the entire genome to identify small RNA (micro-) RNA molecules involved in mute XCI and X genes.

The team tested whether blocking MIR-106A can weaken the silencing effect and “wake up” a sleeping healthy gene. To this end, they used the self-made model of the mouse team Rett I Gene therapy Vector developed by Professor Kathrin Meyer in the National Children’s Hospital. The vector provided a special molecule based on DNA, which acts as a “sponge”, attracting MIR-106A. The molecule reduces the availability of MIR-106A in the X chromosome, which provides a therapeutic window for activation of genes and production of MECP2.

Impressive results

The results were very impressive: treated mice lived longer and showed better movement and cognition than untreated. The study also showed a significant improvement in the irregularity of breathing of treated mice.

“The sick cell contains our own medicine. Thanks to our technology, we simply make it aware of its ability to replace a defective gene with a functional gene,” Bhatnagar explained. “Even a small amount of this gene expression (activation) has a therapeutic benefit.”

Importantly, the Rett Mice model coped well with treatment.

“Our approach based on gene therapy focused on calming the X chromosomes showed a significant improvement in several symptoms of Rett syndrome,” said Bhatnagar. “Girls from Rett show a wide range of symptoms, limited mobility and communication skills. They have apnea and convulsions. It would be changing life if we could reverse some of their symptoms so that they could speak if they are hungry or walk to drink. What if we can prevent these seizures and episodes of apnea, or just reduce them?”

Rett syndrome still has no cure. In the case of families affected by the Rett syndrome, this discovery brings hope that treatment can change life one day. This approach can also work under similar conditions caused by genes combined with X.

Before going to clinical trials, scientists must conduct safety tests to further assess the treatment force and the right dose.