Today at the International Meeting for Autism Research (IMFAR), Autism Speaks Weatherstone Fellow Rylan Allemang-Grand described how magnetic resonance imaging (MRI) could be used to track treatment response to gene therapy in future clinical trials for Rett syndrome.
Mr. Allemang-Grand is pursuing his Autism Speaks research project –
“Monitoring treatment-induced neuranatomic changes in a mouse model of Rett syndrome” – at Toronto’s Hospital for Sick Children.
Rett syndrome affects primarily girls and produces a progressive and debilitating form of autism that includes loss of language and motor control as well as profound medical problems. Its symptoms stem from a defective copy of a gene called Mecp2. Mecp2 is known as a “master gene” because it regulates the activity of many other genes vital to development and health.
Because a defective Mecp2 gene has such broad effects, many experts agree that gene therapy may offer the best chance for treatment.
Though gene therapy for Rett syndrome could be years away, in 2007 geneticist Adrian Bird showed that, in theory, the syndrome could be reversed by restoring or replacing the Mecp2 gene. He did so by creating a genetic off-on switch in mice. This allowed him to keep the Mecp2 gene turned off during the mouse’s development to cause the animal equivalent of Rett syndrome. When he then switched the gene on, it partially reversed the disorder's symptoms – even in severely affected adult mice.
In his IMFAR presentation, Mr. Allemang-Grand described how, using MRI brain scans, he was successful in tracking how activation of the Mecp2 gene in Rett-syndrome mice restored normal brain development – at least in some parts of the brain. His results went further than previous research by showing that some parts of the brain respond much more strongly to reactivation of the Mecp2 gene than do others. “It may be that we need other targeted treatments to rescue certain parts of the brain,” he said.
In addition, Mr. Allemang-Grand found that reactivating the Mecp2gene when the mice were just 50 days old produced a stronger response (greater increases in brain volume) than did waiting until the mice had reached adulthood at 80 days. This may indicate that “the earlier the better” when it comes to gene therapy for Rett syndrome.
Comments Autism Speaks Interim Chief Science Officer Mathew Pletcher:
“It’s encouraging to see that the gene therapy approach continues to show great promise as a transformative therapy for some subtypes of autism, even after childhood. If these approaches are going to be approved for use by people with Rett syndrome, we will need non-invasive methods to measure the benefit that the therapies would producing. Rylan’s research is an important step on the path to a possible clinical trial.”
For more on gene therapy for Rett syndrome, also see this past news coverage:
Gene therapy reverses Rett syndrome in animal model
Experimental diet supplement eases autism-like behaviors in mice
For more coverage from IMFAR 2016, click here.