A Nice Impact Moment for the Simons Foundation on Autism

It must be a pretty sweet gig to be a higher-up at one of these foundations. You play with wads of money, you stick your neck out for a risky but promising study, and every once in awhile, one of the guys (or gals) you fund does something brilliant. And then you get to stand in the shadows, tucking your chin quietly and feeling proud.

That might be about how Alan Packer feels right now. He’s a senior scientist at the Simons Foundation, and some of the research this funder underwrites just had one of those breakthrough moments all the big foundations dream of. David Sulzer, PhD, neurobiology professor at Columbia University Medical Center just discovered a key difference—what could turn out to be the key difference—between autistic brains and nonautistic brains.

And it all comes down to pruning. No, really. As a brain matures out of childhood, it prunes out synapses. A lot of synapses. In late childhood, around age 9 or so, a child’s synaptic density declines by 50 percent—and this is normal. Meanwhile, in autistic children, the synaptic density decreases only around 16 percent, all because of a defective mTOR protein.

Related: Simons Foundation: Grants for Brain Research and Treatment

When mTOR is overactive, the synapses don’t get cut as they should, and autistic behaviors are the result. This has been demonstrated in mouse models. What’s also been demonstrated is the efficacy of a drug called rapamycin in actually eliminating autistic behaviors in mice: The drug blocks overactive mTOR, and makes an autistic brain function normally.

"The fact that we can see changes in behavior suggests that autism may still be treatable after a child is diagnosed, if we can find a better drug," said Sulzer, noting that rapamycin’s side effects in humans might make it unfit for use.

But what’s really incredible here is the level of coincidence at play. That for all the hundreds of genes linked to autism, the end result of these faulty genes is the same: overactive mTOR and screwy self-pruning in the brain. "The current view is that autism is heterogeneous, with potentially hundreds of genes that can contribute," said Alan Packer, Simons senior scientist. "That's a very wide spectrum, so the goal now is to understand how those hundreds of genes cluster together into a smaller number of pathways; that will give us better clues to potential treatments."