Funding innovative collaborations to transform paediatric precision medicine

New research aimed at developing ground-breaking treatments for children with rare diseases, cancers and neurodevelopmental disorders have been funded by Luminesce Alliance.

Investment of more than $300,000 in the three 12-month innovation projects as part of our precision medicine Enabling Platforms strategy, has the potential to revolutionise the understanding and treatment of conditions including blinding eye disease, Rett syndrome and hard to treat cancers.

“These innovative, collaborative research projects bring together experts working towards our mission of transforming the prevention and treatment of childhood illnesses,” said Luminesce Alliance Executive Director Anastasia Ioannou. “Collaboration is the cornerstone of Luminesce Alliance – our partners pool their collective expertise to provide the critical mass needed to work towards transforming paediatric research.”

Genetic drivers of  Rett Syndrome

Associate Professor Wendy Gold, Head of the Molecular Neurobiology Research Laboratory at Kids Research will lead a study aimed at unlocking the mystery of the rare severe neurodevelopmental disorder Rett syndrome. Her team will use integrative approaches to investigate the disease drivers of the disorder, as well as improving methods of predicting its severity and responses to treatments.

Rett syndrome is a rare severe neurodevelopmental disorder, caused by variants in a gene known as MECP2. It causes babies to lose movement and communication and affects one in 10,000 children, mainly girls, including 430 in Australia. The syndrome is hard to diagnose and is often confused with autism or mitochondrial disease as girls with Rett syndrome have symptoms that overlap with characteristics of these disorders.

Researchers around the world are desperately looking for a treatment for Rett syndrome, but despite many clinical trials, there is no cure. One of the reasons clinical trials have failed is that no clinically useful biomarkers have been identified for Rett syndrome.

The new study – Integrative omics: A novel approach to unravelling the complex panoramic landscape – aims to identify disease drivers, drug targets and clinical biomarkers that can predict disease state, disease severity, and treatment efficacy.

A/Prof Gold said the ultimate aim is for clinicians to be able to test for these biomarkers to aid in the diagnosis, and for scientists and pharmaceutical companies to have a reliable measure of disease improvement in clinical trials.

Read more about A/Professor Gold’s Luminesce funded research

Other investigators collaborating on this project include Dr Mark Graham, CMRI, Adviye Ayper Tolun, SCHN, Ashley Hertzog, SCHN, A/Prof Carolyn Ellaway, SCHN, Alexander Wykes, CMRI, Florencia Haase, SCHN, Dr Brain Gloss, WIMR.

New drugs to treat childhood cancers

A study looking speeding up and streamlining the discovery of new drugs to treat childhood cancers will be led by Associate Professor Paul Ekert who is group leader of Computational Biology at the Children’s Cancer Institute (CCI).

Outcomes for children with the most difficult-to-treat cancers remains dismal due to the lack of effective standard treatment options. Combining big data, computational strategies and novel experimental approaches in the laboratory, the project aims to identify molecular drivers of childhoods cancers, potentially leading to new treatments targeting specific genes.

This project will address a critical gap in this process by using computational biology methodologies to sift the vast amount of genetic information being generated about childhood cancers.

“Over the last four years, CCI has collected and profiled the genetic make-up of over 500 high-risk paediatric tumours through the Zero Childhood Cancer Program,” A/Prof Ekert said.

“This provides us with an unprecedented dataset, from which we can gain insight into the specific molecular features and potential drivers of some of the most intractable paediatric cancers.”

Other investigators collaborating on this project include Dr Antoine de Weck, CCI, Dr Ian Street, CCI, A/Prof Greg Arndt, CCI, Dr Antoinette Anazodo, SCHN, Dr Rebecca Poulos, CMRI, Dr Tim Failes, CCI.

Read more about the Luminesce Alliance Computational Biology research

Restoring vision using stem cell transplantation

Restoring the vision of patients with blinding eye disease using stem cell therapy is the aim of the third study, led by Dr Anai Gonzalez Cordero, Group Leader Stem Cell Medicine at the Children’s Medical Research Institute (CMRI).

Millions of people worldwide live with severe degenerative diseases of the eye leading to progressive vision impairment and eventually total blindness. The majority of these inherited and acquired degenerative diseases affect the light-sensing tissue at the back of the eye, the retina, that contains the rod and cone photoreceptors and are untreatable.

The study will further Dr Gonzalez Cordero’s research into the possibility of restoring vision using stem cell transplantation.

“We have demonstrated proof-of-concept for the transplantation of mouse and human stem cell-derived photoreceptors to rescue visual perception in mice,” she said. “In this project, we will move this therapy closer to implementation.”

Read more about Dr Gonzalez Cordero’s research

Other investigators collaborating on this project include Prof Patrick Tam, CMRI, Dr Ngaire Elwood, Murdoch Children’s Institute.

Continue reading “Funding innovative collaborations to transform paediatric precision medicine”

Posted in Uncategorized

Making sense of big data to cure childhood cancers

Our computational biology program is using massive super computers to help make sense of big data to improve the lives of children with cancer.

Our investment in computational biology is contributing to better treatments for children with high-risk cancers. 

The team brings together data from the genome and other biological measurements and compares these data to healthy children and other children who have had similar cancers before. This helps to work out where possible problems might be — and what treatments have worked in the past.

 

The team has developed the first precision medicine data platform that brings together a range of analytical and statistical tools to enhance the treatment of children with high-risk cancers.  

Huge data sets, including known genetic variations, drug responses, and clinical information from thousands of patients, can be analysed and interpreted to provide recommendations for individual patients – with the potential to provide more accurate diagnosis and treatment options. 

Over several days, the computers compare the normal genome of a patient, derived from analysing a blood sample, with that of the tumour from the patient, derived from a biopsy.

Using a database of patients who have had this type of cancer previously, the software then identifies the genetic changes most likely to be implicated in the cancer — and what the best treatment approach is likely to be.

 

The results of our Paediatric Precision Medicine Computational Biology Program will have global implications for the management of children’s cancers. As an integral part of the Zero Childhood Cancer Program (ZERO) — a trial that combines medicine, technology, and research to provide personalised medicine for children and young people with cancer —the team is analysing the genomic data of all children with high-risk cancer across Australia. 

This work has underpinned ZERO’s success in identifying the genetic basis of disease in more than 90 per cent of cases. 

 

“The dream is that every patient gets optimal treatment informed by every patient that’s been before them. We’ve developed innovative analysis tools and an online data portal which lets cancer experts identify the medically relevant pieces so that we can inform precision medicine recommendations” says Associate Professor Mark Cowley, Lead of the Computational Biology Group at the Children’s Cancer Institute.

Luminesce Alliance has catalyzed the creation of Australia’s largest computational biology group solely focused on paediatric cancer It has allowed us to set up the ability to analyse precision medicine data at national-scale for every Australian child with cancer. 

Posted in Uncategorized

Fishing for biomarkers for Rett syndrome

Researchers around the world are desperately looking for a treatment for Rett syndrome, a severe genetic disease that causes babies to lose movement and communication. It affects one in 10,000 children, mainly girls, including 430 in Australia.

Rett syndrome is hard to diagnose and is often confused with autism or mitochondrial disease as girls with Rett syndrome have symptoms that overlap with characteristics of these disorders.

Our project is sifting through more than 700 chemicals found in the blood and urine of girls with Rett syndrome to see whether they are different from those in children without the disease.

These chemicals, called metabolites, could one day be measured in a simple test that would help doctors in their diagnosis, and test whether the disease is progressing, or treatment is working.

Our findings will be invaluable for scientists around the world who are looking for treatments for Rett syndrome, by providing a reliable measure of whether their therapy is working.

It often takes around four years for families to receive an accurate diagnosis of Rett Syndrome. There is no effective treatment for the condition, despite numerous national and international clinical trials.

One of the reasons clinical trials have failed is that no clinically useful biomarkers have been identified for Rett syndrome. 

Luminesce Alliance funding is being used to analyse blood and urine samples from girls with Rett syndrome to find biomarkers – molecular indicators of the disease’s severity and progression.  

The study is searching for biomarkers among more than 700 metabolites (chemicals) in the samples, using state-of-the-art technologies that can identify any disruptions in these chemicals in one test.  

Dr Wendy Gold, Head of the Molecular Neurobiology Research Laboratory at Kids Research, says the ultimate aim is for clinicians to be able to test for these biomarkers to aid in the diagnosis, and for scientists and pharmaceutical companies to have a reliable measure of disease improvement in clinical trials.  

“We would like to find a biomarker that is expressed at a different level between Rett patients and non-Rett patients. Then we can measure whether it changes with disease progression and treatment.”

As well as this ‘fishing expedition’ to look for biomarkers, Dr Gold and her team are studying two specific biomarkers known to indicate mitochondrial stress, which they believe from laboratory tests could also indicate disease progression in Rett syndrome.

The project will determine whether these biomarkers can help diagnose the stage and severity of Rett syndrome in girls and whether they can predict the course of the disease.

“Traditionally, research funders don’t like fishing expeditions – they want to see preliminary data first. Now we have shown there are fish out there, and hopefully, this funding will enable us to catch them.”

 

 

Posted in Uncategorized