By Meaghan Casey
Across the U.S., an estimated 1 of 54 boys (1 of 88 children overall) are diagnosed with autism. For Natick residents Chris and Kate Supple, those statistics were dramatically higher: 2 of 2.
The Supples’ older son, Stuart, was diagnosed with autism in 2005. Just a year later, they found out that their second son, Timmy, is autistic as well.
A brain-development disorder, autism is characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. In the Supples’ case, 10-year-old Stuart is more conversational and attends public school, while Timmy, 9, is nonverbal and attends private school.
“Timmy’s been more significantly impacted,” said Chris. “The may have the same genetic issue, but they’re as different as siblings can be.”
Autism can be reliably diagnosed at 24 months and, in some cases, 18 months.
“Stuart was a late talker and walker, but every infant has his own pace,” said Kate. “We didn’t notice much amiss until Timmy was born. Stuart was 15 months at the time, but not really reacting to his new brother.”
“After that, we were hypersensitive to Timmy and started the ‘autism watch’ much earlier,” said Chris.
While early detection and intervention are critical to improving outcomes, for families, the cause of the disorder remains a mystery. Searching for answers, the Supples sought out private genetic testing, which revealed that both boys carry the same mutation in a gene called neuroligin 4 (NLGN4), which produces a protein critical to communication between neurons.
“We had no history of autism in either family, so we wondered why we went 2-for-2,” said Chris. “If we only had one child, we probably wouldn’t have been as curious.”
The Supples reached out to Dr. Thomas Südhof, professor of molecular and cellular physiology at Stanford University School of Medicine, who had already been studying mutations in the related gene, neuroligin 3, also tied to autism. Südhof and his colleagues published a journal article in 2009 concluding the genetic alteration caused Stuart and Timmy’s autism, but they are still working to determine how and why. He and his team are now analyzing it on two fronts: They are breeding mice that will have the same alteration, and they are recreating it in vitro using the boys’ skin cells that are reprogrammed into stem cells and then brain cells. The neurons will provide different but complementary information about the function of neurologin 4 and how it will react to therapeutic drugs.
Südhof, who has been studying the Supples’ genes for more than five years now, was awarded the 2013 Nobel Prize in Physiology or Medicine in October. He also received the 2013 Albert Lasker Basic Medical Research Award, which is among the most respected science prizes in the world. He received the awards for his work exploring how neurons communicate with one another across gaps called synapses. The work is fundamental to understanding and treating autism and other disorders of brain development.
“We’d like to understand how synapse communication leads to learning on a larger scale,” said Südhof. “How are the specific connections established? How do they form? And what happens in autism when these connections are compromised?”
The Supples met Südhof for the first time this fall when he was in Boston for a fundraiser they organized in support of his research.
“He had just won the Nobel, so it was extraordinary to be able to celebrate that with him,” said Kate. “And it was wonderful for him to finally meet the boys.”
Throughout the years, Stuart and Timmy have participated in five clinical research studies, but Südhof’s is the first pre-clinical study they have been a part of. Currently, clinicians can identify the genetic basis of autism spectrum disorder in 10 to 20 percent of cases. Those figures are expected to grow dramatically in the coming years as genetic discoveries continue to accelerate.
“The challenge is to get more parents to do genetic testing and to get those private results into a public database,” said Kate. “Even if our boys’ alteration is rare, there could be other common pathways leading to some medicines. We see some really cool treatments for symptoms every day. It’s exciting to think of treatment for the disease.”
Autism Speaks, the world’s leading autism science and advocacy organization, is doing its part to try to meet that challenge. In 2011, the organization launched a collaboration with the world’s largest genome sequencing institution, BGI (formerly Beijing Genomics Institute). The Autism Speaks-BGI 10K Genome Project builds on the work of Autism Speaks Autism Genetic Resource Exchange (AGRE), a collection of more than 12,000 anonymous DNA samples from families affected with autism. In July, investigators released results from the project’s pilot study, which focused on 32 families affected by autism and identified autism-linked gene changes—including four new autism-risk genes and eight suspected ones—in 16 of the families.
“The fact that we found notable genetic variants in half of the families reflects our new ability to apply genome sequencing to find those missed in other approaches,” said the study’s senior author, Dr. Stephen Scherer, senior scientist and director of the Centre for Applied Genomics at The Hospital for Sick Children and director of the McLaughlin Centre at the University of Toronto. “This could allow for earlier diagnosis and treatment, particularly among siblings of children with autism.”
Since it was established in 2005, Autism Speaks has funded more than $173 million in scientific research to investigate the causes, diagnosis, and treatments of autism. It is also dedicated to increasing awareness of autism spectrum disorders and advocating for the needs of individuals with autism and their families Chris serves on the board of the New England chapter of the organization and is chair of its advocacy committee.
“With people like Dr. Südhof and organizations like Autism Speaks, I’m certain there will be great progress made,” said Chris. “We just don’t know if it will be in five years or 25 years, or in any time period significant for my kids, but we remain hopeful.”