The Isabella and Marcus Foundation, in partnership with Cure Brain Cancer Australia, are funding the Australasian participation in the ‘International BIOMEDE (Biological Medicine for Diffuse Intrinsic Pontine Glioma Eradication) study’ (2018-2020). This clinical trial is treating 24 children in Australia and New Zealand newly diagnosed with DIPG as part of a worldwide cohort of 250 children. The study is evaluating the efficacy of 3 drugs in combination with radiotherapy. The choice of drug is determined by the mutation(s) found in a biopsy of each child’s tumour. Each drug specifically acts on one type of mutation commonly found in DIPG. The study is being run by the Australian and New Zealand Children’s Haematology/Oncology Group and led by Dr Geoff McCowage at the Children’s Hospital at Westmead, Sydney.
The Isabella and Marcus Foundation is a member of the International DIPG Collaborative, one of 27 like-minded charities around the world that collaborate to fund DIPG projects. The annual contribution from the Isabella and Marcus Foundation supports Australian researchers and the 2019 International DIPG Symposium in Sydney.
The Isabella and Marcus Foundation provides seed funding for DIPG projects, providing researchers with an opportunity to start research that wouldn't otherwise be funded. The data generated can then be used to apply for large government grants that will accelerate research to develop treatments for DIPG and other Diffuse Midline Glioma's.
Dr Misty Jenkins
Walter and Eliza Hall Institute of Medical Research
Immunotherapy is an exciting recent development for the treatment of cancer, with proven efficacy for a number of cancers. Dr Misty Jenkins and her team of researchers from the Walter and Eliza Hall Institute of Medical Research is developing a type of immunotherapy called CAR-T cell therapy, which supercharges the child’s own immune system so that it can effectively destroy DIPG cells. The treatment will involve taking a sample of blood from the child, purifying the immune cells, which are re-engineered in the laboratory to recognise and kill DIPG cells and then infused in large numbers into the child.
Dr Lee Wong
Dr Wong specialises in telomeres, which are complexes found at the ends of chromosomes that are absolutely essential for maintaining chromosome stability. Each time a cell divides, telomeres become shorter and when the cells have gone through many divisions the telomeres become so short that the cells die. This is a protective mechanism against cancer because mutations can accumulate after many cell divisions. However, in some cancer cells, the telomeres do not shorten because an enzyme called telomerase is expressed at higher than normal levels or because a series of molecular events called "Alternative Lengthening of Telomeres (ALT) is turned on. This ALT pathway is common in brain tumours. Most children with DIPG express a mutation that is associated with the ALT pathway. This study investigated the link between this mutation in a Histone 3.3 gene and switching on the ALT pathway.
Jeff is preparing pre-clinical models of DIPG that recapitulate the disease that occurs in children. In its first iteration the model will incorporate the 2 most common mutations observed in children, which are thought to drive the development of the tumour. These mutations, H3.3 K27M and p53 have been genetically introduced into the DNA of the model and sit alongside the normal genes, which are functional until they are replaced by the mutated genes by introducting tamoxifen into the drinking water. A reporter gene, also under the control of tamoxifen, has also been introduced to highlight the area(s) of the brain that express the mutations.
All of the genetic modifications have been introduced. The model is now being evaluated to determine if the mutations trigger the development of DIPG. The model will then be provided to a central repository as a resource for all DIPG researchers worldwide to help fast track treatments.
This work is co-funded by Brainchild Foundation.
Dr. Jason Cain
The Hudson Institute
Jason has studied tumours derived from children with DIPG by growing these cells in the laboratory. In addition, studies of alternative models of DIPG were prepared by directly implanting tumours into the brainstem, allowing the study of the dynamics of the tumour growth in vivo. The tumours were observed to be very slow growing.
DIPG tumour tissue is limited and, due to the treatments received by children, typically harbour additional mutations to those that caused the cancer. Jason has worked to develop new in vitro models of DIPG to provide a continuous source of cells for study, including embryonic fibroblasts, fetal astrocytes (brain cells) and neuronal stem cells, which are suggested to be the source of DIPG.
Brain Cancer Biobank
Brain cancer researchers need ready access to samples for study. Tissue specimens from children are rare and finding appropriate samples in institutions around the country is difficult. Procedures to access samples also differ across the various institutions. Linking the various biobanks across Australia into a single network and portal will enable research by providing ready access to specimens.
‘Brain Cancer Biobanking Australia’ is an initiative of Robyn Leonard (Founder) whose daughter Lucie died from brain cancer. The Isabella and Marcus Fund is supported this initiative until from 2016 to 2019.
The charity regularly sponsors scientific meetings that bring DIPG researchers together to share their knowledge. Scientific exchange provides an impetus for scientific progress. In 2019, the Isabella and Marcus Foundation sponsored (i) the International DIPG Symposium in Sydney (Aug 2nd - 3rd), (ii) the Childhood Cancer Research Symposium at the Hudson Insitute (Feb 13th), and (iii) Cell Signalling and its Therapeutic Implications 2019: Focus on Cancer (May 13th - 15th)
Funding for paediatric brain cancer has historically been low and is why there is no curative treatment for DIPG. From a low funding base it is difficult to attract more funding, creating a ‘Catch 22’. The majority of funding for DIPG research is currently being provided by philanthropic organisations, providing seed funding to drive new research that would otherwise go unfunded.
A corollary to this is a shortfall in scientists that study DIPG. In addressing this the charity is providing PhD scholarships to graduate students who will become the next generation of paediatric brain cancer scientists. These scholarships are named in memory of children who have died from DIPG. 7 scholarships are currently funded with more planned for 2021. These scholarships are funded by the charity’s long-term association with Upstream Foundation.
The Isabella and Marcus Foundation is a member of a the 'Low Survival Cancers Alliance' committee, chaired by the Cancer Council Victoria. The committee advocates for increased funding for cancers with 5 year survival rates below 50%. In Victoria, these cancers represent 20% of all cancer diagnoses but encompass 50% of cancer deaths.
The committee was established in March 2016. Advocacy resulted in $1.5 million in funding by the Victorian government, which was backed by a further $1 million dollars from the Cancer Council of Victoria.
In June 2017 the Isabella and Marcus Foundation presented to the Federal Senate Select Committtee investigating Funding for Research into Cancers with Low Survival Rates.
Professor Peter Rogers University of Melbourne
Conventional radiotherapy is a routine palliative treatment for children with DIPG and provides a temporary reduction in symptoms. Children typically receive 30 treatments over 6 weeks. But conventional radiotherapy is not curative and no other treatments are available. Microbeam radiation therapy is a novel, experimental radiotherapy in which X-rays are generated from a synchrotron. This form of radiotherapy delivers higher doses of radiation in a SINGLE treatment and the beams are shaped to reduce damage to the healthy tissues of the brain. It is being investigated as a curative treatment for DIPG and has shown early promise.
This study demonstrated that doses 20 times higher than conventional radiotherapy could be delivered safely. This exciting finding paves the way for additional studies in preparation for future clinical trials.
This pilot project comprised a multidisciplinary group including physicists, radiotherapists and cancer biologists. A follow up study will occur to examine the efficacy of this treatment for DIPG relative to conventional radiotherapy.
Low Survival Cancers Alliance