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Gene Therapy Reverses Rett Syndrome in Animal Model

Results advance progress toward potential treatment for syndrome characterized by autism and profound medical problems
August 21, 2013


The success of a gene-therapy study in mice has advanced progress toward a potential cure for Rett syndrome, one of the most physically disabling forms of autism. The report appears online today in the Journal of Neuroscience.

Rett syndrome affects mostly girls. It produces a regressive form of autism along with extreme anxiety, lost speech and motor control, severe breathing and digestive problems and other profound medical issues. All these symptoms result from mutations in an X-linked gene called MECP2. A “master gene,” MECP2 regulates the activity of many other genes.

"Gene therapy may be suited for this devastating disorder," comments Autism Speaks Senior Vice President for Scientific Affairs Andy Shih. “Because the Rett gene has many effects throughout the genome, there is no single target for a potential drug. The best chance for treatment is to correct the underlying genetic defect."

In 2007, University of Edinburgh geneticist Adrian Bird demonstrated that, in theory, Rett syndrome could be reversed by restoring the function of the MECP2 gene. He did so by creating transgenic mice in a way that allowed him to turn off the gene during their development to cause the mouse equivalent of Rett syndrome. When he then switched the gene on, its restored function reversed the disorder's symptoms - even in severely disabled adult mice.

This told scientists that gene therapy might someday offer a cure for Rett syndrome in children and adults who have already developed the condition. Typically, gene therapy uses a virus to insert working copies of a gene into cells throughout the body.

One step closer to clinical trials
Molecular biologist Gail Mandel, of Oregon Health and Sciences University, led the new study.  Her team used an altered version of the “common cold” virus that could cross the body-brain barrier to deliver its genetic cargo to brain cells. The entire MECP2 gene was too large for the virus to carry. So the research team gave it only the gene's most critical segments.

The treated mice showed profound improvements in motor function, tremors, seizures and compulsive movements. In addition, the gene therapy restored their abnormally small brain cells to normal. One Rett symptom did not respond to the therapy – abnormal breathing. Correcting Rett’s breathing difficulties may require that gene therapy reach more cells within the brainstem, the researchers propose.

Dr. Mandel cautioned that important steps – including safety studies – remain before this gene therapy is ready for clinical trials with human volunteers.

The mom behind the research …
Much of the financial support for the study came from the Rett Syndrome Research Trust. Its executive director, Monica Coenraads, is the mother of a teenage daughter with the disorder.

“Being the parent of a teenaged daughter severely incapacitated by Rett syndrome and also the person at the helm of RSRT's research program gives me a unique perspective,” Ms. Coenraads says. “As a parent, I bring to the table relentless urgency and a ‘leave no stone unturned’ mentality. My scientific role gives me insight into the painstaking, methodical, rigorous work that needs to be championed to achieve our mission.”  

“The work published today excites me on both levels,” she adds. “More basic science needs to be done to maximize the degree of reversibility and to ensure safety. I want to assure my fellow parents and everyone who loves a child with Rett that we will push on all fronts with the goal of getting to a clinical trial.” 

Autism Speaks has funded and continues to fund research on Rett syndrome and other genetic syndromes associated with autism. You can explore these and all the research Autism Speaks is funding using this website’s Grant Search.

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