Children newly diagnosed with the devastating genetic condition Spinal Muscular Atrophy (SMA) now have access to novel new gene therapy, Zolgensma®, free of charge, after it was listed on the Pharmaceutical Benefits Scheme.

Announced today by Federal Health Minister Greg Hunt, Zolgensma®, which normally costs $2.5 million per treatment, now joins two other publicly funded therapies on offer for SMA – Nusinersen and risdiplam.

The devastating genetic motor neurone disease, spinal muscular atrophy (SMA), quickly paralyses babies, who survive on average 9 to 10 months. While their brains remain unaffected, they lose the ability to move, feed and ultimately breathe. SMA affects one in 10,000 births and was once the leading genetic cause of infant death.

Patients at the Sydney Children’s Hospitals Network participated in the global SPR1NT trial, which investigated the use of Zolgensma®. The study, funded by Luminesce Alliance, followed each participant until aged 18 months, found that all children achieved the ability to sit independently, all were alive and free of permanent ventilation and all had normal swallow function and were fed exclusively by mouth by 18 months of age.

Since the addition of SMA to the NSW Health funded newborn screening program almost four years ago, more than 330,000 babies have been tested for the condition free of charge and given quick access to treatment and support.

Read more: A success story of translation: screening babies nationally for spinal muscular atrophy

“We know that early identification is vital in the treatment of SMA and that is what the newborn screening program has allowed us to do. It has radically shifted our model of care and we are now in a position where we can rewrite the history of SMA,” says Associate Professor Michelle Farrar, paediatric neurologist at Sydney Children’s Hospital and the University of New South Wales, Sydney.

Read more from Sydney Children’s Hospital Network

 

In a collaborative effort supported by Luminesce Alliance, clinicians and researchers have worked together to introduce a molecular test for a previously untreatable disease that paralyses babies.

The devastating genetic motor neurone disease, spinal muscular atrophy (SMA), quickly paralyses babies, who survive on average 9 to 10 months. While their brains remain unaffected, they lose the ability to move, feed and ultimately breathe. SMA affects one in 10,000 births and was once the leading genetic cause of infant death.

We supported a successful pilot that added the first genetic test to the Newborn Screening Program in NSW and the ACT. All babies are now screened for SMA and inherited immune disorders.

New treatments are also revolutionising the outlook for babies with SMA. However, the treatment is most effective when given before a baby develops symptoms – by this time they may have already lost 90 per cent of their nerves. The best way to identify babies who need the treatment is to screen at birth.

“Every day counts. Any delay could be the difference between a child living in a wheelchair or not,” says Associate Professor Michelle Farrar, paediatric neurologist at Sydney Children’s Hospital and the University of New South Wales, Sydney.

“Families now have two birthday parties – one to mark the day the child was born, and the other the day they got their treatment. Before it was uncommon to celebrate first birthdays.”

The power of working together

In a collaborative effort supported by Luminesce Alliance, specialists from Sydney Children’s Hospital Network and the University of  New South Wales universities have worked together to have a molecular test for SMA included in the newborn screening test offered to all 100,000 babies born in NSW and the ACT each year.

Newborn screening involves taking three drops of blood from a newborn baby’s heel. This is then analysed using biochemical tests for more than 25 medical conditions.

International gene therapy trial

The impetus to test newborns for SMA was boosted by an international gene therapy trial, including NSW children, which indicated a single dose of gene therapy could potentially reverse the disease.

With world-leading expertise in SMA, newborn screening and gene therapy, the members of Luminesce Alliance realised there was an opportunity to show international leadership in this space. They launched a pilot of the first genetic test to be included in the newborn screening program.

The new test involves extracting the baby’s DNA from the heel prick test and looking for genetic variants that indicate SMA as well as some primary immunodeficiencies. The test is highly specific and sensitive and can be conducted on-site at Westmead.

If a baby’s genes suggest they may have a form of SMA, further tests can be conducted to confirm the diagnosis and start life-saving treatment.

Making the test available to babies throughout Australia

The two-year pilot was completed in 2020 and was then continued with NSW Health funding. The data were analysed by the Federal Government, which recently recommended that newborn screening for SMA should be implemented nationally.

The pilot boosted the case with implementation and health economic data that showed newborn screening for SMA was value for money, led by Prof Georgina Chambers from the National Perinatology Epidemiology and Statistics Unit.

A/Prof Farrar says this work would not have been possible without the connections, reputation and organisational support offered by Luminesce Alliance.

Read more: Testing & treating newborns for spinal muscular atrophy: saving lives & healthcare costs

 

By Kathryn Greiner, Luminesce Alliance Chair

A few years ago, patients presenting every year to our children’s hospitals in Australia with serious inherited conditions often resulted in no diagnosis or cure.

The international explosion in genomic medicine has offered new hope of identifying the genetic cause of these diseases and finding targeted therapies to treat them – an advance called precision medicine. But there needs to be an organised, systematic way of introducing this model of care into the health system.

Luminesce Alliance was funded in 2018 by the NSW Government to create a paediatric translational research hub delivering twenty-first-century precision medicine for the families of NSW.

We brought together NSW’s leading paediatric medical research institutes with our children’s hospitals network and universities to combine strengths and capabilities, creating a competitive advantage in paediatric research that was previously lacking in NSW.

With a strong translational focus, we have been able to fast-track discoveries in the laboratory into treatments for patients with rare diseases and cancer, sometimes in a matter of months.

Medicine that uses the power of genomics can be astonishingly successful. Rather than the incremental benefits we would normally expect from medicine, these new therapies have the potential to completely cure children of their condition.

The strength of Luminesce Alliance is in the collaborations it nurtures – collaborations between fiercely competitive research institutes and clinical campuses, between different research teams, between clinicians and scientists, and between people from a wide range of disciplines. The way these teams are now working together is, perhaps, our greatest achievement.

NSW is now at the international vanguard of paediatric precision medicine – but there is still so much more we could do. We want to develop new treatments in NSW for our children and families, and export them to the world. Through nurturing paediatric research, our modelling shows we can attract even more investment to NSW, create jobs, and generate government cost-savings through the rapid diagnosis and treatment of childhood disease.

The discoveries being made will have impacts far beyond child health. Improving diagnosis and treatment of children will support families and communities, boost the economy through saving on health expenditure in later life, and lead to new understandings that will be applied to many common adult diseases in future.

Learn more about our research projects

 

New opportunities towards gene therapy and diagnosis for the blinding eye disease, retinal dystrophy, may now become available following work done by the Eye Genetics Research Unit at the Children’s Medical Research Institute.

The team looked at the RPGR gene which is involved in maintaining healthy photoreceptor cells. Variants in this gene are the main contributor to eye disease such as rod cone dystrophy and gene therapy for this condition is now in clinical trials.

The research, published in the Journal of Personalized Medicine, was partly supported by Luminesce Alliance funding.

The team worked closely with collaborators at the Department of Clinical Genetics and Sydney Genome Diagnostics, Western Sydney Genetics Program, Sydney Children’s Hospitals Network (SCHN), and the Rare Diseases Functional Genomics Laboratory, SCHN, and CMRI, and Save Sight Institute, Faculty of Medicine and Health, University of Sydney.

Find out more about this research

 

A new test for genetic diseases is successfully providing the sought-after answers for families of sick children. RNA diagnostic testing has already achieved a diagnosis for more than 70 families, with hopes it can be implemented in everyday clinical practice.

Current methods using DNA sequencing are only able to diagnose half of the children and families with suspected genetic disorders. Professor Sandra Cooper from Kids Neuroscience Centre (KNC) at Kids Research says the importance of a diagnosis cannot be overstated. She has developed standardised RNA testing procedures to deliver patients with a precise molecular diagnosis.

Find out more about this research

Prof Cooper leads SpliceACORD, the Australian Consortium for RNA Diagnostics, with a vision to implement these standardised practices in routine clinical medicine. This research was supported by Sydney Health Partners and Luminesce Alliance and recently published in Genetics in Medicine.