Finding cures for children's genetic diseases


New trial could give hope to kids like Jerry

An Australian world-leading gene therapy expert believes the future of medicine for children with rare diseases who often “slip through the cracks’’ is in personalised treatments.

Dr Leszek Lisowski is Head of the Translational Vectorology Research Unit and Manager of the Vector and Genome Engineering Facility at Children’s Medical Research Institute in Sydney. It is the only lab of its kind in Australia and one of only a few in the world.

His work is highly technical, but his personal approach is led by the heart.

“What I’m trying to do is build individualised treatments for children who have ultra-rare conditions—this is where my heart lies.’’

It is work such as this that may help save the life of children such as three-year-old Jerry Ong, from Gippsland, in Victoria.

Jerry was born with an extremely rare condition known as SPG50–associated hereditary spastic paraplegia – a mutation (error) of the AP4M1 gene. The progressive condition means he will soon lose his hard-won ability to crawl and to walk as his legs become more and more stiff and weak. He may never speak, and his brain will continue to deteriorate.

Jerry’s parents, Bess and Dave Ong, hope gene therapy will reverse the progression and are fundraising for a clinical trial that might help save their youngest son’s life.

“Dr Lisowski’s research focuses on gene-therapy technology, which could deliver the cure for this insidious disease by halting the disease process and preventing the faulty gene from further damaging Jerry’s brain and body,” Ms Ong said. 

“The research has turned up exciting results, and clinical trials are possible. But they’re expensive and health dollars are stretched, especially during a pandemic. We have joined the effort to raise money to support this research. Every dollar counts.”

Dr Lisowski creates microscopic delivery vehicles, called vectors, which make gene therapies possible. The vectors deliver gene therapeutics into patient’s cells affected by the disease. The therapy adds a working copy or replaces the faulty copy of a gene with a functional version.

Gene therapy aims to cure, not just treat, genetic disorders by correcting the mutations. In the past, his work has been used for genetic diseases that impact the hematopoietic system or the liver, but now he is hoping to start a new project working to help young patients, such as Jerry with devastating neurological disorders.

“We will use a viral vector to deliver a functional copy of the SPG50 gene to the patient’s brain,’’ Dr Lisowski said. “We will make pre-clinical models, using organoids (mini human organs), and we have a state-of-the-art organoid facility right here at CMRI, led by Dr Anai Gonzalez-Cordero, an emerging leader in the field.”

Organoids are mini organs that are grown in labs to test out therapies. The team at CMRI will use brain cells to test their therapy before trials can begin.

“While the knowledge and diagnostic power around genetic disease has grown exponentially, the progress in disease prevention and treatment has been slower. Gene therapy has the power to fill the gap, and to bring real benefits to patients,” he said.

Gene therapies are relatively new additions to the healthcare toolbox but are already saving lives by curing previously incurable conditions.

“Infants who would otherwise have succumbed to devastating neurological disorders are now developing normally with the very real prospect of living full and healthy lives,” he said.

“This is an exciting and a very rewarding time to be a researcher in the area of gene therapy. We are hoping to be able to deliver this treatment to children within two years. It could even be faster.’’
While incredible work is being done around the world on truly devastating diseases, those with rarer conditions like Jerry are often forgotten.

Dr Lisowski wants to devote his work to helping families like Jerry’s.

“This condition is ultra-rare and most government or commercial funding would not go towards a condition like this; they often slip through the cracks. To help this family really aligns with my own personal values. We want to help people that aren’t being helped, to find those who are being overlooked.’’

If you would like to support the work of Dr Lisowski, you can donate to a Jeans for Genes fundraising page set up by Jerry’s family to directly fund the work being done in Dr Lisowski’s lab.