Protecting children receiving chemotherapy from hearing loss

Researchers at Ear Science Institute Australia have developed a novel nano-gel therapy to protect children receiving chemotherapy from hearing loss – a common side effect of the cancer treatment.

The project which involves testing the nano-gel in a new study is led out of Ear Science Institute Australia and supported by funding from the Channel 7 Telethon Trust.

A much-needed preventative approach

Lead researcher, Associate Professor Hani Al-Salami, said about half of children who go through chemotherapy will have some degree of permanent hearing loss due to toxicity of the drugs.

“There is currently no proven prevention or cure for this hearing loss, so this new research will test the effectiveness of a nano-gel that is injected into the ear before chemotherapy to prevent the possible side effect of cancer treatment among children,” Associate Professor Al-Salami explained.

“The nano-gel has been developed in partnership with Curtin University by a group of clinicians, pharmaceutical scientists, ENT (ear, nose and throat) surgeons, cochlea physiologists and synthetic chemists using cutting-edge technologies.

“Human bile extract is put through specialised systems to produce a gel, which is capable of being injected into the human ear. It can potentially protect children from the side effects of chemotherapy, which targets and destroys cancer tissues and can also kill other healthy tissues resulting in problems including hearing loss.”

Associate Professor Hani Al-Salami in the lab
Associate Professor Hani Al-Salami in the lab

Looking forward

Ear Science Institute Australia CEO, Sandra Bellekom, said it was a very exciting time for ear and hearing medical research in Western Australia.

“The Telethon grant will allow Ear Science to further develop an established and proven nano-gel, improving efficacy and making it safer for use in our children,” Ms Bellekom said.

The Channel 7 Telethon Trust’s support of Ear Science Institute Australia also includes funding for the procurement of a newly developed scanning electron microscope for use in the research, which is capable of micro and nano scale visualisation of critical features of the nano-gel.

Predicting relapse in children with cancer

Research at Children’s Cancer Institute has already led to a highly accurate test to predict relapse in children with leukaemia. Now, an equivalent test for children with solid tumours is on the horizon.

Testing for ‘minimal residual disease’

When an Australian child is diagnosed with the blood cancer, acute lymphoblastic leukaemia (ALL), their doctor is almost certain to make use of a DNA-based technique called minimal residual disease (MRD) testing. The test works by detecting and measuring the level of leukaemia cells that remain in the child’s body after treatment begins, and is a powerful predictor of relapse. But for children diagnosed with solid tumours, no such test is available − yet.

‘The key to identifying children at high risk of relapse is to be able to detect even the tiniest quantities of minimal residual disease, as early on in their treatment as possible,’ explained Professor Murray Norris AM, who led the team that developed molecular technology so sensitive it is capable of detecting one leukaemic cell in a million normal cells.

‘This gives the child’s doctor an opportunity to alter treatment well before relapse occurs.’

Professor Norris

When tested in clinical trials, the Institute’s MRD technology led to an effective doubling in survival rates in children with high-risk ALL, and it now underpins tailored treatment strategies for children diagnosed with ALL throughout Australia.

Developing an MRD test for solid tumours

Recent research, published in the British Journal of Cancer, suggests we are getting close to having the equivalent of an MRD test available for children with solid tumours.

Led by Dr Toby Trahair, Clinical Research Fellow at Children’s Cancer Institute and paediatric oncologist at the Kids Cancer Centre, Sydney Children’s Hospital, the research shows that whole genome sequencing (WGS) technology can be used to identify tumour-specific markers, which can be used to detect cancer cells that have survived treatment and will lead to relapse if allowed to do so.

‘To find out if we could use WGS technology as the basis of MRD testing for solid tumours, we looked at data from the Zero Childhood Cancer Program (ZERO), Australia’s first personalised medicine program for children with cancer,’ explained Dr Trahair.

‘ZERO involves extensive molecular analysis of children’s tumours, including WGS, and has given us access to the kind of data we’ve never had before.’

Dr Trahair

‘Our results strongly suggest that using WGS to identify tumour-specific gene sequences is going to lead to a very accurate and reliable way of detecting and measuring MRD in children with solid cancers. And while our research focused on high-risk neuroblastoma and Ewing sarcoma, we believe the findings are likely to be applicable to multiple types of cancer.’

Australian first gene therapy for childhood blindness

Two Sydney siblings have become the first patients in the country to receive a novel gene therapy that has rescued their vision and holds hope for preventing them from going blind.

The ocular gene therapy, LUXTURNA, is the world’s first approved gene replacement therapy for an inherited blinding eye condition and one of the first gene replacements for any human disease. Approved by the Therapeutic Goods Administration, LUXTURNA is used to treat children and adults with biallelic pathological mutations in RPE65, a rare mutation that leads to vision loss and blindness. It is being distributed in Australia by Novartis.

Therapy has stopped progressive vision loss

Seventeen-year-old Rylee and 15-year-old Saman were both diagnosed with Leber congenital amaurosis, a severe form of retinal dystrophy, in their first year of life. They received the life-changing therapy at The Children’s Hospital at Westmead in late 2020 and early 2021. The therapy has stopped their progressive vision loss and led to some improvements in their vision.

The therapy was delivered as part of Ocular Gene and Cell Therapies Australia (OGCTA), a new collaboration involving the Genetic Eye Clinic at Sydney Children’s Hospitals Network (SCHN), the Eye Genetics Research Unit and Stem Cell Medicine Group at the Children’s Medical Research Institute (CMRI), and the Save Sight Institute at Sydney Eye Hospital and University of Sydney.

CMRI’s Gene Therapy Research Unit

Revolutionary therapy

CMRI was represented on this project by Professor Frank Martin who is CMRI’s Board President, Professor Robyn Jamieson, Head of the Eye Genetics Research Unit at CMRI and SCHN and Dr Anai Gonzalez Cordero, Head of the Stem Cell Medicine Group and Professor Ian Alexander, Head of the Gene Therapy Research Unit and their teams.

Professor Jamieson is also lead of OGCTA and Head, Specialty of Genomic Medicine, University of Sydney. She said the therapy was revolutionary and would lead to transformation of care for patients with blinding eye diseases.

Professor Robyn Jamieson

“Inherited retinal disease is a devastating diagnosis. Up until now, these patients suffered progressive vision loss that led to blindness and there was no therapy for them at all.”

Professor Jamieson

“But through new genomic diagnostics and the use of ocular gene therapy, we are finding that we have the ability to not only stop this ongoing progression but also help to improve vision for people who have RPE65-related retinal vision loss.”

Children and adults born with a mutation in both copies of the RPE65 gene can suffer from a range of symptoms, including night blindness (nyctalopia), loss of light sensitivity, loss of peripheral vision, loss of sharpness or clarity of vision and potentially total blindness.

Replacing faulty genes

Ocular gene therapy works by injecting LUXTURNA under the retina and carrying a functioning RPE65 gene to replace the faulty one, thereby preventing some of these devastating symptoms.

luxturna Team – the team who delivered Australia’s first gene therapy for a blinding eye condition

“The real-world improvements in visual function has been quite remarkable bringing to life the rather dry clinical trials outcome measures,” said Professor John Grigg, Head of Specialty of Ophthalmology, Save Sight Institute, University of Sydney and lead inherited retinal disease specialist in OGTCA said.

“It is tremendously heartening to see the changes in vision capabilities for these first patients treated with LUXTURNA.”

Professor Grigg

“As an ophthalmologist who has been caring for patients with Leber’s amaurosis for many years and unable to offer any treatment, it is incredibly rewarding to now have the opportunity to not only give families hope but also be involved in improving their child’s vision,” said Frank Martin, Clinical Professor in the Specialties of Paediatrics and Child Health and Ophthalmology at the University of Sydney said.

Associate Professor Matthew Simunovic, Vitreoretinal Surgeon, Sydney Eye Hospital and SCHN and Associate Professor at the Save Sight Institute, University of Sydney performed the first surgery and said the benefits of treatment should extend well into the future.

“This is incredibly delicate surgery in which LUXTURNA is injected under the retina, which in some patients can be as thin as a sheet of copy paper. Riley and Saman have had profound improvements in their vision, which mirror the results seen in the pivotal clinical trials.”

“Importantly, such benefits appear to be sustained for many years – in fact, for as long as patients have been followed up. Successfully delivering the first approved gene therapy has been a fantastic team effort, and it underscores Australia’s capability in this field.”

A/Prof. Simunovic

To date, this treatment has been used to treat four patients and while it can only be used to treat this specific form of retinal disease, it does provide significant hope that similar treatments will be able to be applied to other retinal disease genes in the future.

“This heralds a new era in transforming the lives of these people who otherwise have a life of blindness ahead of them and provides hope for more than 15,000 other affected Australians who live with some form of inherited retinal disease,” Professor Grigg said.

Read more about this story on ABC News.