There is a growing body of evidence that autistic spectrum disorders (ASD) are the result of miswiring within the developing brain, leading to connectivity problems. To test this hypothesis, Mustafa Sahin and his team at Children's Hospital Boston studied a rare disorder called tuberous sclerosis complex (TSC) which is often associated with ASD.
TSC is caused by defects in either the TSC1 or TSC2 genes. It is now known that the TSC1 and TSC2 gene products inactivate an enzyme called mTOR, which in turn controls neural growth. This corroborates Sahin’s data from 2008 showing that disrupting TSC1 and TSC2 caused neurons to sprout two or more axons, rather than the single one that normal neurons have. More recently, they found that disrupting TSC2 prevented mouse retinal axons from mapping correctly from the retina to the visual area of the brain. Instead, the neurons continued to grow past the point where they should have stopped.
The next step was to examine the brains of humans. Sahin and his colleague Simon Warfield used diffusion tensor imaging (a type of MRI) to examine the brains of 10 TSC patients, (7 with autism or developmental delay), and 6 unaffected controls. The researchers found abnormal and poorly myelinated axons in the TSC sufferers.
Can anything be done with this new data? Possibly. There is a drug called rapamycin which is an inhibitor of mTOR. In fact, mTOR stands for ‘mammalian Target of Rapamycin’.
Rapamycin is already FDA approved to prevent organ rejection in transplant patients. In mouse studies, abnormal neurons that had been growing multiple axons reverted to only growing one axon when presented with rapamycin. Rapamycin even normalized myelination in mice.
Although these results seem promising, we won’t know whether this treatment will yield any benefits until more data is collected. Sahin plans to launch a clinical trial of rapamycin in TSC patients later this year.