Tackling a family of conditions as complex as the various autism spectrum disorders (ASDs) will require a concerted effort between scientists, clinicians and funding organizations—as well as patients and their families. Panelists at Wednesday afternoon’s session on “Whole Genomes and Autism” described how such collaborations are leveraging sophisticated technology to map the genetic landscape of the ASDs as a means for achieving earlier diagnosis and targeted treatment.
Three talks focused on initiatives supported by Autism Speaks, a leading advocacy organization for the ASD community. First, Stephen Scherer of the Hospital for Sick Children described his team’s efforts with the MSSNG program, which endeavors to fill in the many blanks in our current understanding of the genetic foundations of ASD. “We know there are 100 or more different genetic forms of autism,” said Scherer. “For roughly 20% of families, molecular genetic markers can be identified.” His group has sequenced the genomes of nearly 9,000 individuals with ASD from different families, and have already homed in on 61 relevant genes. Critically, all of this data—and other associated medical information—is hosted on the cloud, so that other interested researchers can draw on it.
Harvard Medical School neuroscientist Mustafa Sahin followed with an overview of his effort to understand how these ASD-associated genes work. The Preclinical Autism Consortium for Treatment (PACT) employs carefully designed and validated animal and cell-based models to generate starting points for drug discovery and development. “We want to focus on mutations that have been shown with relative robustness in human populations to be associated with ASD [and] on symptoms that are relevant to the core features of autism,” said Sahin.
The Autism Treatment Network was designed to help translate these research findings into the clinical pipeline, and Thomas Frazier, Chief Science Officer at Autism Speaks, described how his organization is rallying the autism community to accelerate this effort. In addition to hosting data for researchers, MSSNG also offers a portal for families that have contributed their data to connect with scientists and each other. “The idea… initially, at least, was that we would give folks back their genetic results, but then we realized that there’s a much larger opportunity here,” said Frazier. “We can connect them around medical findings, behavioral findings or even things like age and developmental level.” This also allows individuals to continue to contribute to the data collection process, building a rich resource for clinical trial recruitment. Frazier’s team is now focused on broadening the network’s geographic and demographic coverage. “This is ideal for personalized medicine trials of these rare genetic syndromes,” he said, “[because] any individual site may only have one or a handful of patients with these syndromes.”
The panel concluded with a presentation from Mark Gurney, Chairman and CEO of Tetra Discovery Partners, who described how his company has partnered with the FRAXA Research Foundation to develop a promising drug for one of the ASDs, Fragile X syndrome. Their work built on academic research that flagged an enzyme called PDE4D as a likely culprit in the disorder, and Tetra subsequently developed a PDE4D inhibitor that delivered striking results in mouse models. “We see amelioration of most of the behavioral phenotypes,” said Gurney. “We see normalization of social interaction and other mouse behaviors.” The company is now starting a phase 1 trial, and expects to treat its first patient later this month.