Finding new, targeted therapies for childhood neurodevelopmental disability

Each year, approximately two in every 1,000 children in Australia are born with cerebral palsy. In some cases, the disorder is genetic and Professor David Amor, consultant clinical geneticist and inaugural Lorenzo and Pamela Galli Chair in Developmental Medicine at the University of Melbourne, is unravelling the gene variants that cause cerebral palsy to provide individualised, targeted treatments.

“The traditional paradigm is that cerebral palsy results from an accident during pregnancy or at birth, but over the past five to ten years we’ve shown that 20 to 30 percent of cerebral palsy is genetic,” says Professor Amor, who also heads the Neurodisability and Rehabilitation Group at the Murdoch Children’s Research Institute (MCRI).

Professor David Amor.

“Some cerebral palsy is caused by a single gene fault. Our team has discovered some of these genes and we can test children in our clinic who don’t have an obvious explanation for cerebral palsy. We sequence their genome with a simple saliva swab and look across hundreds of different genes known to be a potential cause.”

When there is cause for concern, Professor Amor’s vision is for a child to be tested within the first weeks and months of life.

“We can then identify specific causes of cerebral palsy and tailor treatment, such as a new drug that targets a particular pathway. Implementing effective precision therapies at the earliest stage can alter the natural trajectory of cerebral palsy and change a child’s future,” he says.

Dr Kylie Crompton works with Professor Amor and is a Research Fellow and Clinical Trials Manager at MCRI who is particularly focused on working with families of children with cerebral palsy.

Dr Kylie Crompton.

“Our focus is on a combined effort on how to assess interventions to improve quality of life,” says Dr Crompton.

“At the moment our research is primarily in sponsored trials. Those trials didn’t used to come to Australia but in the past five years we’ve seen them increase because from a regulatory, costing and expertise perspective we are now set up. But we have also reached a point where we are ready to take on investigator-initiated trials, too – studies initiated by our own researchers and clinicians and we hope to see those trials bear fruit in the next few years.”

With Professor Dinah Reddihough, Dr Crompton previously led an investigator-initiated Australian-first trial that found collecting and storing cells from a baby’s umbilical cord and later transferring them to a sibling who has cerebral palsy was safe.

While there is no cure for cerebral palsy, cord blood cells have the potential to improve brain injury and gross motor function because of their ability to activate repair processes and regenerate some tissues in the human body.

Current trials under way within the Neurodisability and Rehabilitation Group at MCRI by Professor Amor and Dr Crompton include medication trials for children with du15q syndrome, autism and irritability combined and with autism and social withdrawal. The Group also recently joined a study for children with Angelman syndrome.

“Our broader vision is focused on targeted treatments of neurodevelopmental disability. At this point we have management strategies and non-specific supporting treatments but our aim is to have new targeted treatments and to be able to implement effective precision therapies at the earliest possible stage,” says Professor Amor.

“We are world leaders in Australia in genetic testing and in the epidemiology of cerebral palsy. But research is an international community and we are working with people all around the world and sharing ideas.”