New research to block the action of damaged genes may reverse rare and devastating childhood illnesses

Illustration of brain and DNA

It is one thing to track down and define genetic disorders, but it’s another to work on developing the kinds of interventions that may well stop these neurological disorders in their tracks. 

In a new research paper published in Nature Portfolio Journal of Genomic Medicine this month, a team of researchers led by Adelaide University has outlined a first step in developing the DNA tools to switch off the progression of some of the toughest and previously most mysterious neurological disorders.

The research relied on genetic material from siblings who had suffered a rare condition that saw these healthy born children deteriorate and die before the age of 10 years, progressively losing mental and physical capacity since the first symptoms appeared.

Head of neurogenetics at the University of Adelaide, Channel 7 Children’s Research Foundation Honorary Chair for the Prevention of Childhood Disability and Australian NH&MRC Senior Principal Research Fellow, Professor Jozef Gecz, believes the research is a giant leap towards making such severe disability not only preventable, but also treatable.

“We know from genomic research that about one in 5000 people have the risk gene for this condition and are otherwise healthy,” Prof Gecz says.

“The cause of the disorder is minuscule, that is one single DNA unit alteration, which sits in so called junk DNA of a gene, TIMMDC1, crucial for energy metabolism. The consequences of the alteration are major and result in failure to thriveretardation of psychomotor development, low muscle tone, and severe neurologic dysfunction.

“Our work uses splice-switching oligonucleotides (SSOs) - short, synthetic, antisense, modified nucleic acids that can 100 per cent restore proper assembly of the TIMMDC1 gene, which is otherwise messed up by the genetic alteration and 99 per cent non-functional.”

Senior postdoctoral scientist and lead investigator for the project, Dr Raman Kumar 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.”Senior postdoctoral scientist and lead investigator for the project, Dr Raman Kumar.

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

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 and 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 and 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.

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