Nine-year-old twins Jobe and Tate are alike in every way except one: Jobe has a rare condition called Sanfilippo syndrome, a form of childhood dementia. Jobe’s development began to slow at 18 months. Shortly after, he was diagnosed with the disease, caused by mutations in genes responsible for processing large sugar molecules.
Kids like Jobe face difficult, heartbreaking lives cut short by the illness. At 9 years old, Jobe has forgotten how to draw a circle, write his own name, and struggles to recall the names of his loved ones. “It’s like grieving your child’s life in front of your eyes, before they’ve even started it,” his mother said in a statement. “There’s not a day that goes by that you don’t wake up and think about this terrible disease and wish that there was a cure—not just for Jobe, but for the kids yet to be born.”
The parents of those kids may now gain a better understanding of the disease, thanks to new research published in Nature Communications. Using stem cells derived from patients with Sanfilippo syndrome, neuroscientists from the South Australian Health and Medical Research Institute and Flinders University created cortical circuits to study how synaptic activity differs in those with disease.
Read more: “Saving the Girl with Dementia”
The neurons functioned normally at first, but as they matured they showed hyperactive excitatory synapses, disrupted network dynamics, and dysregulated gene expression. “What we see in these children’s neurons is an escalation of excitatory activity that overwhelms the brain’s natural balance,” study author Cedric Bardy said.
In other words, during early brain development, the neurons go into overdrive and stay that way.
They also found that this overactivity could make the neurons more vulnerable to stress. Depriving the neurons of nutrients accelerated the overactivity, suggesting other physiological stressors like childhood disease could speed up disease progression. “Our research shows that disrupted synaptic communication is not simply a byproduct of degeneration. It is an early driver of the disease,” Bardy said.
While there’s currently no cure for Sanfilippo syndrome—as well as limited treatments available—advances in stem cell and gene therapy could give families hope. Until then, research like this can at least help parents better understand the debilitating disease afflicting their children. 
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Lead photo courtesy of SAHMRI
