Emily Singer

Rainie Henson has three sons with autism, a 20-year-old and 16-year-old twin boys. Three years ago, the boys’ psychiatrist, Dr. Craig Erickson at Cincinnati Children’s Hospital in Ohio, told her about a clinical trial he was running to test a new medicine for autism. Her family had never participated in clinical research, but Henson was intrigued.

The drug had shown early promise in treating fragile X syndrome, a genetic condition linked to autism. Scientists thought the medicine, currently approved to treat alcoholics, might help in some general cases of autism as well.

Developing and testing new drugs for autism can be quite challenging. Autism has no clear physical symptom, such as high blood pressure or cholesterol level. So it’s difficult to measure success. Moreover, the condition is incredibly diverse. A drug that helps some people with autism may not help others. If a drug fails in clinical trials, it’s often unclear whether the drug is broadly ineffective or if it might have worked if tested in the right group of people.

Henson’s sons reflect that diversity. She enrolled her three boys in the 12-week trial, to mixed results. The drug had little impact on her eldest, but it did seem to help the twins. Henson says that within a few weeks, their speech improved and repetitive behaviors subsided.

Erickson and others haven’t yet reported the outcome of the study. It’s unclear whether the medicine will help others as it did the Henson twins. But the study represents a growing trend in autism research: a search for medicines that might get at the underlying biology of the condition. Scientists hope that research into specific genetic conditions associated with autism, such as fragile X, will help guide that process.

A GAME CHANGER

Autism therapies potentially fall into two general categories: those that treat the core symptoms of autism (social challenges, communication issues and repetitive behavior), and those that address behavioral issues and other things that can accompany the condition, such as irritability and attention deficit hyperactivity disorder (ADHD). To date, no approved drugs target the core symptoms. But a few drugs can help some secondary symptoms.

Risperadone and aripiprazole can help with irritability and agitation, which can sometimes prevent otherwise cognitively capable children with autism from being placed in typical classrooms. Treating ADHD can help children with autism in other domains, such as learning, says Jeremy Veenstra-VanderWeele, a psychiatrist at Columbia University in New York. “For some kids, that’s been a true game changer.”

Tests of other promising treatments are under way. A number of ongoing trials are studying oxytocin, a hormone that plays a role in human bonding. Scientists think it might help people with autism by helping them pay greater attention to sources of social information, such as body language or eye contact. Previous studies have shown that oxytocin can increase eye contact, but the studies are small and the results inconsistent.

“The question is whether it changes behavior in a way that’s helpful to people with ASD,” says Veenstra-VanderWeele, who is involved in a large clinical trial of oxytocin in people with autism, the SOARES-B study. Results from his and other studies are likely to come out in the next year or so. “I think they will be really exciting,” he says.

Veenstra-VanderWeele is also searching for ways to make existing drugs safer. Risperadone and aripiprazole have a potentially dangerous side effect: serious weight gain. Veenstra-VanderWeele and collaborators have found that metformin, a drug typically used to treat diabetes, prevents drug-linked weight gain in children with autism. “That changes things substantially for kids where those medicines are necessary but weight gain and other medical risks prevent their safe use,” Veenstra-VanderWeele says.

TARGETING THE CORE

Drugs such as oxytocin and metformin may help people with autism. But they don’t target the biology behind the condition. It’s unclear, for example, whether people with autism have problems with their oxytocin system. “We may find medications that make a person more likely to want to spend time with another person,” Veenstra-VanderWeele says. “But that’s not something that is a problem for everyone, though social motivation is clearly lower in some people with autism.” Similarly, scientists may find drugs that decrease repetitive behaviors in autism without getting at the root causes of that behavior.

What’s still lacking in autism therapies are “transformative treatments based on neuroscience,” Veenstra-VanderWeele says. Scientists have learned a great deal about the biology and genetics underlying autism. They are now trying to parlay that information into new treatments, an approach called translational research.

The greatest advances to date come from studies of genetic syndromes linked to autism, such as fragile X syndrome, an inherited form of intellectual disability. Scientists know the specific genetic changes that cause this disorder. They can create mice with the same genetic changes and then study the resulting changes in the brain and in behavior.

In 2012, scientists showed that an experimental drug could improve both brain function and behavior in mice with the fragile X mutation. But similar drugs have had mixed results in humans. (The drug being tested in Erickson’s study in Cincinnati acts on the same pathway.) The animal studies are promising, “but we haven’t seen that those treatments work in the same way in people with fragile X,” Veenstra-VanderWeele says.

Some evidence suggests the drugs work in a subset of people with autism, highlighting the challenges of testing new treatments for a condition as diverse as autism. Researchers hope to identify genetic or other markers that can predict which children are likely to respond to the drug. (For in-depth examination of the challenges of clinical trials in autism, check out Why don’t we have better drugs for autism?, from Spectrum.)

Veenstra-VanderWeele cautions that translational research for autism is still in its early stages. “Before the game starts, everyone thinks they’ll get a hit on the first swing,” he says. “We do everything we can to prepare so we can hit the ball out of park, but it turns out that’s not realistic.” Just as it takes time to learn to hit a baseball, scientists need to make multiple attempts before finding the right approach to treatment. “But I still think we will eventually be able to make a substantial difference for subsets of kids where we really understand the neurobiology,” he says.

GETTING INVOLVED

Fragile X is just one of several genetic disorders linked to autism. Scientists know there are many genetic risk factors for the condition. Currently, roughly fifteen percent of individuals with autism have an identifiable genetic cause. In most cases, scientists don’t yet know how those different risk factors affect the brain and behavior.

SPARK aims to help fill that gap by identifying genetic mutations in SPARK participants and then linking participants to relevant clinical research. “It allows us to have clinical trials based on a biological understanding of the genetic risk,” says Veenstra-VanderWeele, who is affiliated with one of SPARK’s clinical sites. “I think that’s incredibly important.”

Families who are interested in participating in clinical trials have a number of options. Those who see physicians in academic medical centers can talk to their doctors about local studies. Support groups and organizations specific to each condition, such as fragile X, often inform members of new research opportunities. Alternatively, the website clinicaltrials.gov lists all ongoing trials in the country. The site can be somewhat overwhelming, so families may find it helpful to talk to clinicians they already trust, Veenstra-VanderWeele says. SPARK participants will eventually be informed of relevant clinical trials.

“Participating in research can be helpful for some families,” Veenstra-VanderWeele says. “They feel like they are making a difference, not just for themselves but for others.” He cautions that it’s important to find clinicians with a research background for advice. (All projects that seek to recruit participants through SPARK will be reviewed and vetted.) “Some people are well meaning but make promises that aren’t based on evidence,” he says. “Try to find someone in an academic medical center who can give you a research paper that shows that a treatment works.”

Related Articles:

Oxytocin:

• Questions for Larry Young: Oxytocin’s promise for autism
• Oxytocin’s power
• Mouse study bolsters case for oxytocin in autism

Fragile X:

• Studies highligh promise of fragile x treatment
• Questions for Eric Klann: Translating treatments for fragile X

Phelan-McDermid:

• Growth factor shows promise for Phelan-McDermid syndrome

Early Behavioral Intervention:

• Researchers seek ‘active ingredients’ of early intervention
• Early intervention yields big benefits for children with autism
• The controversy over autism’s most common therapy

Clinical Trials:

• Why don’t we have better drugs for autism?
• Why trials of autism treatments have a placebo problem
• The innovators: How families launch their own autism studies
• Better behavioral tests may save trials of autism treatments