A wide spectrum narrows

SOUTHBOROUGH, Mass.—SynapDx, a start-up, early-stagelaboratory services company, has obtained an exclusive worldwide license totechnology from Children's Hospital Boston for blood-based tests targetedtoward the early detection of autism spectrum disorders (ASDs), developmentalsyndromes affecting one in 110 U.S. births—and four times as many boys asgirls.

The financial terms of the deal, announced May 2, were notdisclosed, but the commercial value of providing a diagnostic autism test wouldbe substantial, according to medical experts and economists.

The National Institutes of Health report that most parentsof autistic children suspect something is wrong by the time the child is 18months old, and seek help by the time the child is two years old. Yet, theaverage age of diagnosis is 4.5 years—rather late to begin the kind ofintensive therapy needed to ready a child for school.

This is partially because pediatricians tend to consoleanxious mothers and adopt a wait-and-see approach. A diagnostic test for autismwould solve that problem, both SynapDx and the hospital believe.

Today, ASDs are diagnosed using a variety of assessmentsthat combine direct patient observation and medical history. The addition of aclinically meaningful blood test could hasten the diagnostic process and helpchildren at risk for ASDs get access to the right evaluations earlier—and endup with better outcomes as they grow, SynapDx says.

SynapDx's initial focus with the technology licensed fromthe hospital will be to develop an assay "targeted at specialists whoevaluate children with possible developmental concerns, to more effectivelydifferentiate children with autism spectrum disorders from those with othertypes of developmental disorders," says Theresa Tribble, senior director ofclinical market development for SynapDx.

The technology being licensed was developed in collaborationwith Dr. Louis Kunkel and Dr. Isaac Kohane at Children's Hospital. Kunkel isthe director of the Children's Genomic Program. Kohane is the director of theinformatics program at the hospital. Both are listed as scientificcollaborators on SynapDx's website, along with Leonard Rappaport, chief ofdevelopmental medicine at Children's Hospital and a professor of pediatrics atHarvard Medical School.

Kunkel describes autism as a developmental disorder thatmost likely involves genes expressed in the brain and probably has both geneticand environmental causes.

"Because many genes expressed in the central nervous systemare also expressed in whole blood, we reasoned that we might be able to findsignatures of gene expression that would allow us to categorize patients withautism and possibly identify causative genes," Kunkel states. "We can nowpredict whether a gene expression profile is derived from a blood sample takenfrom an autistic child or from a control. We are expanding these studies tomany more patients and controls in the hopes of developing a diagnostic testfor autism."

SynapDx also mentions a recent gene expression projectundertaken by Kohane, Kunkel and colleagues. According to the firm, theresearchers investigated 400 ASD cases and controls and ultimately identified asignature that has "robust classification accuracy," the firm says onits website. "These data suggest that differential expression of certain genesin blood cells may form the basis for an ASD biomarker."

The Children's Hospital researchers discussed the study in aposter at the American Society of Human Genetics meeting in November,describing a 245-gene prediction model they said could be used to distinguishASD cases from those with other disorders.

"Our findings suggest that changes in peripheral bloodgene expression reflect those found in the ASD brain, as well as implicate theprocesses of neurodevelopment and immune-signaling in disease," concludedthe researchers.

SynapDx last year licensed blood-based autism detectiontechnologies developed by another scientific collaborator, Valerie Hu, aprofessor of molecular biology at George Washington University. Hu was thefirst to demonstrate that altered RNA expression levels could be interpreted todistinguish between ASD and normal individuals using RNA samples derived fromperipheral blood.

Using lymphoblastoid cell lines established from peripheralblood leukocytes available through the Autism Genetic Resource Exchange, Hu andher colleagues identified gene expression signatures that differentiate betweenASD and normal twins, between affected and unaffected sibling pairs and amongindividuals with different idiopathic ASD diagnoses and unaffected relatives.

SynapDxwas founded last year and closed an undisclosed Series A round of venturefunding in May 2010 from North Bridge Venture Partners, Bain Capital Venturesand General Catalyst Partners. The company is led by President and CEO StanleyLapidus, who previously founded next-generation sequencing firm HelicosBiosciences.