Screening and treatment
By better understanding the numerous routes autism can take to perturbing common pathways, new avenues of treatment might open up sooner. Currently, treatment is based on behavior or serendipity, State says, adding, "we're very far behind other areas of medicine in that respect." But, he says, if a genetic screen can find even a rare mutation in a child before symptoms appear—or even in utero—behavioral therapy could start earlier, improving that child's level of functioning.
And for pharmaceutical development, if treatments can be pinpointed to improving a common pathway, rather than fixing a particular genetic error, they might be able to treat a wider range of ASD patients instead of each individual type of mutation. But interventions like these are "easier said than done," Zoghbi notes. "There are lots of proteins involved and lots of genes involved."
Genetics are, of course, just part of the increasingly complex autism puzzle. "Two people can have exactly the same mutation" and not have the same degree of developmental disorder, State says. "The question of why is the multimillion-dollar question."
To help sort out this increasingly urgent answer, Gregory advocates for a broad-spectrum approach. "It's not going to be one thing, it's going to be a collection," he says. "Between genetic, genomic and epigenetic, we'll identify what causes the spectrum." (Epigenetics refers to the environmental modification of genetic activity; such changes can be heritable.) And within these, the environment is often another complicating factor, as a person's genetic makeup can render them more or less sensitive to environmental influences—whether that is from social bonding or purported chemical influences.
But one thing is well established in autism research: as scientists look deeper into the disease the complexities multiply almost exponentially. Gregory suggests that one of the next steps will be to assess the mechanisms behind epigenetic influences in autism. But "that becomes a harder thing to answer," he says, speaking from experience in that field. DNA methylation and its effect on genes varies in different types of tissue, adding another layer of challenge to parsing the interdependent effects.
The other research teams are also hard at work on the next batch of studies. State's group is expanding their study to include some 1,600 more families as well as homing in on gene regions that they have already found.
The rush of studies in the past couple years has been thanks in large part to technological advances as well as a push to study the disease more closely. "The down payment in the early part of this century is really paying off," State says. But Gregory is eagerly anticipating "the next big leap forward" in higher-resolution sequencing, which will allow is group and others to "identify these very small changes" that researchers are now only just getting a taste of.