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A treatment that targets the genetic defect in tuberous sclerosis prevents autism-like symptoms in mice at 6 weeks of age — the mouse equivalent of adolescence. Researchers presented the unpublished results yesterday at the 2014 Society for Neuroscience annual meeting in Washington, D.C.
The results suggest that it might be possible to block — or even reverse — symptoms in children and teens with autism-related disorders.
Mutations in TSC1 cause tuberous sclerosis, a rare disorder marked by benign tumors and developmental delay. Roughly half of people with tuberous sclerosis also have autism.
Mice missing TSC1 in Purkinje cells, a subset of neurons in the cerebellum, show autism-like symptoms, such as social deficits, restricted interests and repetitive behaviors, at around 2 months of age. The Purkinje cells in these mice fire less frequently than normal and begin to die around the same time that symptoms appear.
A 2012 study showed that rapamycin, an immunosuppressant that inhibits TSC1’s downstream target, mTOR, can prevent these symptoms in mice when started at 7 days of age. But the drug’s effects when given later in development were not known.
In the new study, researchers started the rapamycin treatment in mice at 6 weeks of age. To their surprise, they found that the treated mice do not develop the symptoms. The drug also normalizes the excitatory signaling in Purkinje cells and prolongs their survival.
“This is like treating mice late in adolescence,” says lead researcher Peter Tsai, assistant professor of neurology at the University of Texas Southwestern Medical Center in Dallas. The findings were unexpected, Tsai says. “It suggests that social behavior may be amenable to treatment even into later stages,” he says. “That’s encouraging, and it gives me a lot of hope that delayed therapies may work.”
Treatment at 6 weeks does not prevent restricted interests or repetitive grooming.
Giving rapamycin at 10 weeks of age prevents the autism symptoms in mice missing one copy of TSC1, but not in mice missing both copies of the gene. This suggests that in mice with both copies missing, the disease process is already underway and irreversible with rapamycin treatment, Tsai says.
For more reports from the 2014 Society for Neuroscience annual meeting, please click here.