In the late 1980s, neuroscientist Mark Bear set out to study a cell receptor that appeared to play a role in making connections between neurons in the brain. He was interested in plasticity–the formation, strengthening, and weakening of brain connections that allows us to learn things and form new memories. Finding potential cures for Fragile X syndrome, a genetic disorder that can cause autism, was the furthest thing from his mind. “I had no idea what Fragile X was,” he says. “None.” But 20 years later, Bear’s research led to the extraordinary discovery that shutting off the receptor can reverse the symptoms of Fragile X in mice. Trials for drugs that block the receptor in humans are now under way.
“It was a classic payoff of basic research,” says Bear, a professor of neuroscience at the Picower Institute of Learning and Memory.
Bear ended up studying autism serendipitously, but a growing number of other MIT scientists have set their sights on the condition in recent years as they’ve learned how serious and widespread it is. “Fifteen years ago, autism was thought to be a rare disorder,” says neuroscientist John Gabrieli, PhD ‘87. “People understand much more how common it is–and how difficult it is.”
About one in 110 American children has a disorder on the autism spectrum, which ranges from milder difficulties with communication and social interaction to much more severe deficits that may be accompanied by mental retardation. Children do not “outgrow” autism, but symptoms can improve with treatment, which usually includes a combination of behavioral, speech, and physical therapy. Doctors may also prescribe drugs to treat specific symptoms.
Under the umbrella of the Simons Initiative on Autism and the Brain at MIT, launched in 2009, researchers are tackling autism at all levels–from genes to brain anatomy to behavior. Their work so far has yielded some promising drugs for Fragile X and for a form of autism called Rett syndrome, as well as new devices that could help autistic children learn to cope better with social interaction.
Children with autism appear to develop normally until about the age of two, when they start losing interest in other people, including their parents. They have difficulty making eye contact, reading social cues, and interacting with others, and they tend to exhibit delays in language ability, repetitive behaviors such as rocking, and an obsessive focus on order and routine.
Researchers have known for years that autism may have some genetic basis, and in the past decade they have identified dozens of genes that could be involved. Many of these genes play a role in the development of synapses, connections between neurons that allow them to exchange information. In autistic children, the brain’s ability to make those synapses appears to be impaired early in life–perhaps even before autism symptoms begin appearing. “The first two to three years of life are massively important for forming connections in the brain, and this is when autism strikes,” says Mriganka Sur, head of MIT’s Department of Brain and Cognitive Sciences.
Sur, Bear, and other molecular neuroscientists approach autism as a malfunction of plasticity–the phenomenon that allows the brain to change in response to experience or environment. “Disorders of development are disorders of how the brain is wired,” says Sur. “That’s why autism is so fascinating to me, because it maps so directly onto plasticity.”
About three years ago, Sur began studying Rett syndrome, a rare condition that was linked in 1999 to mutations in an X-chromosome gene that codes for a protein called MeCP2. When neurons don’t have enough MeCP2, which is necessary for nerve-cell maturation, they can’t grow the tiny branchlike projections needed to form synapses. The result is heart abnormalities, seizures, severe speech impairments, reduced head size, and typical autism symptoms, including repetitive hand movements. Most patients are female; boys with the condition usually die before or shortly after birth.