Patient Profile: (Re)Searching for a Cure
Dr. Thomas Südhof, who won the 2013 Nobel Prize for Physiology or Medicine for his work with autism research, meets Timmy Supple, 9. As part of his research, Südhof has been studying the genes of Timmy and his brother Stuart since 2009.
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, their second son, Timmy, was diagnosed with autism as well.
A neurological disorder, autism is characterized by difficulties in social interaction, impaired verbal and nonverbal communication, and sensory integration deficits that can result in repetitive, and often difficult and socially awkward, behaviors. In the Supple family, 10-year-old Stuart has some limited language capabilities and attends public school, while Timmy, 9, is nonverbal and attends a private day school for children with autism.
“Timmy’s much more significantly impacted,” said Chris. “They both have autism, and in fact they both may have the very same medical issue that’s causing their autism, but they’re otherwise as different as two siblings could 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 too much amiss with Stuart until Timmy was born. Stuart was 15 months at the time, and not really reacting to his new baby brother. You hope it’s just delay, and then at some point you’re told it’s
not delay, it’s a disorder.”
“After getting Stuart’s diagnosis, we were hypersensitive to autism with Timmy,” said Chris. “I was certain there was no way Timmy had autism, because as a baby and young toddler he was so alert and engaged. But in his middle-teen months you could start to see it, and then it was clear he was going to get the diagnosis, too, and he did.”
While early detection and intervention are critical to improving outcomes, the cause of the disorder remains a mystery. Searching for answers, the Supples sought out genetic testing, which revealed that both boys carry the same gene alteration in a gene called Neuroligin 4 (NLG4), which produces a protein critical to neuron communication across gaps called synapses.
“We had no history of autism in either family, so it struck us as odd that we went 2-for-2 in the autism lottery,” said Chris. “If we’d had only one child with autism, we probably wouldn’t have been as curious about the medical and biological reasons, but with two we wanted to see if we could get some answers.”
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 alterations in a related gene, Neuroligin 3, which had also been linked to autism. Südhof and his colleagues led a study and published a journal article in 2009 concluding that the NLG4 genetic alteration caused Stuart and Timmy’s autism, but they are still working to determine exactly how, and why. He and his team are now analyzing it on two fronts: breeding mice that will have the same alteration, and 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 NLG4 and how it will react to therapeutic drugs.
Südhof, who has been studying the Supple boys’ genes for more than five years now, was awarded the 2013 Nobel Prize in Physiology or Medicine this past October. He also received the 2013 Albert Lasker Basic Medical Research Award, which is among the most respected science prizes in the world. His 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?”
After a five-year coast-to-coast e-mail relationship, the Supples met Südhof inperson for the first time in October, when the Supples organized and hosted a fundraiser in Boston in support of his research.
“Dr. Südhof had just won the Nobel Prize, so it was extraordinary to be able to
celebrate that with him and for him to finally meet our boys,” Kate said
Outside of Südhof’s independent lab work, Stuart and Timmy have participated in several research studies. Clinicians can currently 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 autism families to do genetic testing and to get those results into a scientifically accessible database,” said Kate. “Perhaps many others with autism have our boys’ same gene alteration, but even if it is rare it could be related to brain pathways that are common across many people with autism. We see some amazing treatments for symptoms every day; but it’s really exciting to think of treatments for the disease itself.”
Autism Speaks, the world’s leading autism science and advocacy organization, is doing its part to try to meet the 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 10,000 anonymous DNA samples and robust clinical information 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 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 of 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 — including Dr. Südhof’s research — to investigate the causes, diagnosis, and treatments of autism. 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 his team at his lab, and organizations like Autism Speaks, we’re 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 our kids, but we’re hopeful. For our family to be a part of something that could bring some relief some day to tens of thousands of families whose lives have been turned upside-down by autism would bring great meaning and value to the otherwise awful impact autism has had on us.”