Research looking at blocking the action of damaged genes

Sometimes all it takes to cause a severe neurological disorder is one tiny defect in a single gene. Unfortunately, there are thousands of these genetic, childhood-onset conditions, and while they are rare, the symptoms can be devastating.

Commonly, these conditions involve a failure to thrive, retardation of psychomotor development, low muscle tone, and severe neurologic dysfunction.

Because the root cause of these neurological conditions is so minuscule, they can be incredibly difficult to diagnose and even harder to treat with the necessary specificity.

A team led by researchers at the University of Adelaide has developed a new DNA-based tool to do just that.

Professor Jozef Gecz, who is the Head of Neurogenetics at the University of Adelaide and the Channel 7 Children’s Research Foundation Honorary Chair for the Prevention of Childhood Disability, believes this research is a giant leap towards making such severe childhood disabilities preventable and treatable.

“Our work uses short pieces of modified DNA that can recognise a mutated gene and use their specific function to 100% restore its proper structure.

We’ve shown that this can work for a mutation in the TIMMDC1 gene which causes severe neurological disability in children.”

Dr Raman Kumar, senior postdoctoral scientist at the University of Adelaide and lead investigator for the project, says the research is significant not only for this genetic illness and the families with this specific alteration, but because it shows an approach that can be applied to many other similarly damaged genes.

“This work sets up an exciting precision genomic medicine path to correct the action of damaged genes and to fully restore their natural function,” Dr Kumar says.

“It brings new hope in the treatment of some of the most devastating childhood illnesses.”

What’s next?

The next phase of the research is being supported by the Channel 7 Children’s Research Foundation.

“We are now moving the research from cells to mouse models before we take it to the next phase and apply the therapy to the affected children,” Dr Kumar says.

“There are thousands of different types of genetic, childhood-onset neurodisabilities which can now be genetically diagnosed. Technologies like this, in addition to genome editing and stem cell-based therapies, offer new hope in providing precision solutions for these illnesses.”

The project team includes researchers from the University of Adelaide’s Medical School, Robinson Research Institute, and Dame Roma Mitchell Cancer Research Laboratories; the Department of Neurology at the Women’s and Children’s Health Network, the Adult Genetics Unit, Royal Adelaide Hospital; The Murdoch Children’s Research Institute; The Royal Children’s Hospital at Parkville, Victoria; the University of Melbourne’s Department of Biochemistry and Pharmacology; and the Institute for Genomic Medicine and Departments of Neurosciences and Paediatrics, University of California.