In a new study, researchers found a new treatment to treat gene-related deficiency in children with autism.
The research was conducted by a team from the Baylor College of Medicine.
Autism is a developmental disorder that affects 1 in 59 children in the U.S. Mutations in specific genes, such as PTEN, can explain many autism cases.
While children with mutations in PTEN exhibit autism, macrocephaly (an abnormally large skull), intellectual disability and epilepsy, there are currently no effective treatment options for children affected by this condition.
In the study, the team showed that a previously unexplored pathway goes awry in the brain of PTEN-deficient mice, and its restoration reverses their behavioral and neurophysiological abnormalities.
More importantly, the researchers developed a new therapeutic strategy to treat the symptoms associated with PTEN-deficiency.
Based largely on experiments with the drug rapamycin, it was widely believed that dysregulation of mTORC1 is responsible for the condition.
However, the team suspected that this was not the entire story since mTORC2 activity was also dysregulated in individuals with mutations in PTEN.
The researchers worked with a model of this condition in which mice were genetically engineered to lack PTEN specifically in neurons, the nerve cells of the brain.
PTEN-deficient mice present with macrocephaly, seizures, shorter lifespan, alterations in social behaviors as well as memory problems similar to those observed in patients with autism spectrum disorders.
The team found that genetically silencing the mTORC1 complex in PTEN-deficiency mice only resulted in the restoration of the size of the brain.
It did not affect survival, the behavioral alterations or even the number of seizures.
Unexpectedly, genetically silencing mTORC2 complex activity resulted in prolonged lifespan, suppressed seizures, the rescue of long-term memory and reduced autism spectrum disorder-like behaviors.
Currently, there is no drug that could specifically inhibit mTORC2. Thinking of possible future clinical applications of these findings, the researchers developed an antisense oligonucleotide, a molecule that silences the activity of mTORC2 by preventing the synthesis of one of its defining components.
When they administered a single injection of the antisense oligonucleotide, they were able to reverse the abnormal behaviors and reduce seizures in PTEN-deficient mice.
Their findings suggest that modulation of mTORC2 activity is a promising treatment.
Finally, mTOR signaling also is altered in other neurological disorders, including epilepsy, tuberous sclerosis, Fragile X syndrome, and Alzheimer’s disease.
Future experiments should determine whether mTORC2 also is the main mTOR complex implicated in these disorders.
One author of the study is Dr. Mauro Costa-Mattioli, a professor of neuroscience.
The study is published in Nature Medicine.
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