DIXDC1 Gene Slows Brain Cell Communication In Autism

A key ‘on’ button in DIXDC1 protein that instructs brain cells to form mature connections called synapses with other brain cells during development has been discovered.

This finding, from scientists at McMaster University’s Stem Cell and Cancer Research Institute in collaboration with Sick Children’s Hospital, provides new insights into Autism Spectrum Disorder (ASD) that will guide identification of new medications for people with ASD. The disorder affects one in 68 individuals, and there are no medications that target the core symptoms of this complex disorder.

The researchers, led by Karun Singh, a scientist with the Stem Cell and Cancer Research Institute (SCCRI), discovered an important ‘on’ button in DIXDC1 protein that instructs brain cells to form mature connections called synapses with other brain cells during development.

Correcting Synaptic Connections With DIXDC1

Working with geneticist Stephen Scherer from The Hospital for Sick Children and the University of Toronto, the team identified genetic changes that keep DIXDC1 turned “off” in a group individuals with autism, predicted to cause brain synapses to stay immature, and reduce brain activity.

“Because we pinpointed why DIXDC1 is turned off in some forms of autism, my lab at the SCCRI, which specializes in drug discovery, now has the opportunity to begin the searching for drugs that will turn DIXDC1 back on and correct synaptic connections,” said Singh. “This is exciting because such a drug would have the potential to be a new treatment for autism.”

While this discovery holds promise, mutations in DIXDC1 account for only a small number of individuals with autism and related psychiatric conditions, Singh said.

“However, there is strong evidence that many other autism genes disrupt the development of synapses similar to DIXDC1; therefore, the key to a new treatment for autism will be to find safe medications that restores brain cell synapse growth and activity.”

Mick Bhatia, director of the SCCRI, said the discovery signifies the institute’s strategic entry into the area of neural disease and genetic guided personalized drug development.

Kwan, Vickie et al.
DIXDC1 Phosphorylation and Control of Dendritic Morphology Are Impaired by Rare Genetic Variants
Cell Reports , Volume 17 , Issue 7 , 1892 – 1904

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