Could autism be reversed with a pill?
What if autism could be reversed with a pill?
A growing body of research in mice and a handful of people is finding that autism is not a degenerative disease like Alzheimer’s, but a changeable condition, like, say, epilepsy that can potentially be controlled.
A study out Wednesday in the journal Neuron found that medication could correct the health and behavior problems of mice with a genetic condition known to lead to autism in people. The drug, which acts on the synapses, or gaps, between brain cells, reversed a vast range of symptoms often associated with autism -- including lack of sociability, physical awkwardness, and hyperactivity.Most surprising, the drug worked on adolescent mice, showing that these symptoms are reversible even after the critical period of early brain development.
“I was thrilled,” said Mark Bear, the MIT neuroscientist who led the research.
Bear helped found a company, Seaside Therapeutics, which is currently studying a similar drug in people with Fragile X, a genetic condition that often leads to autism. The mice had the same genetic change as the people in the study. Roche and Novartis are also studying similar medications, with effectiveness trials due to be completed in about a year.
“I can’t tell you how exciting it is right now, and how anxiously I am awaiting the impact of these clinical trials,” Bear said. “It seems that in Fragile X and maybe other causes of autism there is essentially a metabolic problem.”
The problem in Fragile X, Bear said, seems to be that there are too many proteins being produced in the junctures between brain cells. Flooded with proteins from one brain cell, the receptors at another don’t know which protein to accept, and, essentially, a traffic jam results.
Bear said he was amazed, several years ago, when he realized that a tie-up between brain cells could cause the full range of symptoms found in autism.
“It truly is extraordinary that this receptor seems to give rise to so many aspects of the disease,” he said.
Bear’s isn’t the only research to suggest that autism may be reversible, even beyond childhood.
In a 2007 study in the journal Science (covered in The Globe at the time), Adrian Bird from Edinburgh University reversed symptoms in adult mice with a different genetic glitch -- which leads to another autism-like condition in people, called Rett Syndrome. Using medication to turn back on the gene that is turned off in Rett Syndrome “leads to striking loss of advanced neurological symptoms in both immature and mature adult animals,” Bird’s study concluded.
Last month, another study -- this time in Nature -- found that Rett’s devastating symptoms could be stopped in mice if they got a bone marrow transplant. This suggests that the immune system plays a role in Rett.
Mice with Rett syndrome normally live about weeks, but given a bone marrow transplant from healthy mice, they live much longer -- at least some of them are still alive nearly a year later, said Noel C. Derecki, the research fellow who led the study at the School of Medicine at the University of Virginia.
Derecki, and senior author Jonathan Kipnis, an associate professor at Virginia, said their work suggests that the loss of the MECP2 gene seen in Rett impairs the brain’s ability to “take out the trash.”
“These cells need to be cleaned up, so debris doesn’t build up,” said Derecki, whose grandfather ran a garbage collection business. By reinforcing the immune system with a bone marrow transplant, the researchers restored the mouse brain’s ability to take out the trash.
Again, their conclusion was that autism is likely changeable throughout life -- that the behavior we see in people with autism is due to brain malfunctions but not brain damage.
The next step is to take their research into people, figuring out what kind of treatment will be most helpful. It’s not yet clear either whether the findings in Rett and Fragile X will extend to the roughly 85 percent of those with autism who don’t have an obvious genetic glitch.
Bear says that the findings of reversibility in older animals is good news for drug testing, because it’s much easier to study drugs on adults than children.
Also, he said, a drug alone may not be enough.
Mice given the drug for four months improved far more than those given it for just a month -- suggesting, he said, that the brain needs to adapt once its biological problems have been resolved.
In people, Bear said, “it’s not just the drug that’s going to lift the veil [of autism], but it’s going to allow the veil to be lifted with appropriate behavioral therapy. And that’s really what we’re aiming for.”
Karen Weintraub can be reached at Karen@KarenWeintraub.com.
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