Researchers Discover Possible Key to Affecting Brain of People with Down Syndrome

Down syndrome is the most common genetic cause of intellectual disability, affecting approximately 400,000 Americans and one out of every 691 live births. The genetic cause of Down syndrome has been long known: each of these patients has an extra copy of the 21st chromosome. However, it has never been understood how this extra copy of genes causes intellectual disability in these patients.

Now, for the first time, researchers have identified the changes in gene expression in the brains of people born with Down syndrome. These findings were published in the journal Neuron by a multi-institution team of researchers led by Tarik Haydar, PhD, associate professor of anatomy and neurobiology at Boston University School of Medicine (BUSM) and Nenad Sestan, MD, PhD, professor of neuroscience at Yale School of Medicine. Dr. Haydar and Dr. Sestan’s research groups analyzed the genes that were turned on and off in the brains of patients with Down syndrome, looking at different ages and different regions of the brain. They discovered that there are changes in the genes that affect brain cells called oligodendrocytes. These cells create the brain’s myelin, or wiring insulation in the white matter of the brain. No wiring insulation means slower signaling, which irreversibly alters the brain’s nerve development.

The researchers found this problem most affects their subjects’ brain development from toddlers to adulthood. It was assumed until now that, like most genetic problems, the changes that cause intellectual disability in people with Down syndrome had occurred before birth and could not be changed. The researchers are hopeful that these findings can translate to a gene therapy that can be given to very young patients with Down syndrome to help them insulate their white matter before these irreversible developmental changes occur.

“This discovery of the genetic changes that alter communication within the brain uncovered a completely new target for therapies in the brains of people with Down syndrome,” explained Haydar.  “These findings may allow researchers to design strategies to promote brain functioning and improve quality of life.”

The researchers also believe these findings may have profound implications for individuals with other developmental disabilities, such as autism.

This work was supported by grants NS076503 and MH106934 from the National Institutes of Health and by a grant of the Korea Health Technology R&D Project through KHIDI (HI14C2461). Additional funding was provided by the Kavli Foundation, the James S. McDonnell Foundation scholar award, the Ruth Kirschstein NRSA fellowship (NIH) and the China Scholarship Council fellowship.

Submitted by Ariel Marks, MD.