A world-first clinical trial has given hope to children with arteriovenous malformations, helping young people like Derek walk again.

Fourteen-year-old Derek first came to The Children’s Hospital at Westmead when he started losing feeling in his hands and feet. He could barely walk or lift his arms, and breathing felt like it was through a straw.

Derek was diagnosed with an arteriovenous malformation, or AVM, a condition where tangles of blood vessels form preventing oxygen from reaching nearby tissue. While AVMs can occur anywhere in the body, Derek’s was positioned near his lower brain stem and upper spinal cord.

“My day-to-day life changed heavily. From being able to do everything on my own to then needing my parents to do everything for me,” Derek said.

“Around the house I always needed help to walk and when getting out of the house I had to use a wheelchair.”

Ongoing treatment for Derek’s condition, brought about a collection of side effects including weight gain, kidney stones, and infections.

Derek eventually stopped attending school full time, instead regular hospital visits became the norm.

As his condition worsened with conventional treatments only offering short-term stabilisation, clinicians knew they needed a new approach.

Dr Kartik Bhatia, Paediatric Interventional Neuro-radiologist at the Hospital, turned to his research colleagues to help Derek.

“I had read a new article describing the use of liquid biopsy in adults to help identify the genetic changes present in some venous malformations without the need to take a core needle biopsy,” Dr Bhatia said.

It was known that core needle biopsies have a high risk of life-threatening bleeding if conducted on adults and children with AVMs. A liquid biopsy would significantly reduce bleeding risk.

“With a low-risk liquid biopsy, we could identify the genetic changes of an AVM,” Dr Bhatia said.

“The results of the biopsy could potentially provide targeted treatment to children with AVMs.” 

Dr Bhatia contacted novel liquid biopsy expert, Dr Smadar Kahana-Edwin, Scientific Team Lead of the Advanced Molecular Diagnostics Laboratory at the Children’s Cancer Research Unit at the Hospital.

Their collaboration supported a world-first clinical trial to use liquid biopsy for children and young people with AVMs.

“Liquid biopsies have mainly been used in cancer to detect DNA fragments shed from tumours into the blood,” Dr Kahana-Edwin explains.

“What’s different here is that AVMs aren’t cancers, and we learnt through this study that by drawing blood directly from the vein draining the AVM, something done during a standard treatment procedure, that we could capture enough DNA to pinpoint the genetic changes responsible for these AVMs.”

With the help of Dr Kahana-Edwin, Dr Bhatia and many others, Derek’s medical team were able to identify the genetic changes of his AVM. Based on these genetic results Derek’s clinicians discovered there was an existing targeted treatment that could treat his AVM.

Derek’s treating doctor, Dr Caroline Bateman, Paediatric Haematologist at the Hospital, said that discovery was life changing. 

“The targeted therapy saved Derek’s life,” said Dr Bateman.

“He was having recurrent significant neurological episodes that interrupted normal body functions like breathing. But now, he is out of a wheelchair and planning the rest of his life. He is a very brave young man.”

Derek’s targeted treatment shrunk his AVM and diminished his other severe health symptoms.

“I’m feeling great now,” Derek said. “Being on this treatment has improved and helped me a lot.”

“With this treatment I was able to get back to day-to-day life and get back to doing what I love.”

“I love fishing and cars. Getting out and setting up in front of the water and throwing a line out just brings an escape from everything else. Working on cars, going to car meets. Cars, cars, cars love it all!”

Derek is eighteen years old now. He can walk and breathe easy again.

Derek was one of twelve participants in the clinical trial led by Dr Bhatia, most with significant disability. Out of all the participants, half have started targeted treatments and have seen positive health outcomes as a result.

“I think this method will change the way we treat children with AVMs into the future, not just in Sydney but worldwide,” Dr Bhatia said.

The trial was recently published in the internationally prestigious journal Nature: Communications Medicine.

It shows that collaboration between clinicians and researchers can directly transform the lives of children in hospital, that laboratory research can directly enable hospital bedside treatments.

This research was only possible through the huge collaboration efforts across hospital departments at The Children’s Hospital at Westmead, including medical imaging, oncology, clinical genetics and research. By connecting these specialties, the team were able to integrate liquid biopsy genetic sequencing into real-world health care pathways for children and young people.

The research conducted was also supported by the University of Sydney and Westmead Hospital.