Research funded

The Isabella and Marcus fund provides seed funding for DIPG projects that would otherwise not be funded from government grants. The goal is to provide researchers with an opportunity to access larger sources of funding that will accelerate research for the development of treatments for brain cancer in children.

Associate Professor Jeffrey Mann, Monash University

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 and sit alongside the normal genes, which are functional until birth. Soon after birth the mutations will be triggered by administration of 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 these mutations.

All of the genetic modifications have been introduced. In early 2017 the mutations will be triggered. If DIPG develops the model will be provided to a central repository as a resource for all DIPG researchers worldwide and help fast track treatments.

Jeff 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 harbours 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.

Dr. Lee Wong, Monash University

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.

Professor Peter Rogers, University of Melbourne

Conventional radiotherapy (CRT) is a routine treatment for children with DIPG as a palliative measure and provides a temporary reduction in symptoms. Children typically receive 30 treatments over 6 weeks. But CRT is not curative and no other treatments are available. Microbeam radiation therapy (MRT) is a novel, experimental radiotherapy in which X-rays are generated from a synchrotron instead of a linear accelerator (CRT). 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. In studies published to date, synchrotron MRT has shown equivalent or superior tumour control to CRT in different animal models.

This pilot project comprised a multidisciplinary group including physicists, radiotherapists and cancer biologists. It provided a template for subsequent studies that will determine the optimal dose for DIPG and examine the efficacy of this treatment for DIPG relative to conventional radiotherapy.

Infrastructure: 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 initial phase of the project is now complete.  The Isabella and Marcus Fund is supporting this initiative until 2018.

This project is also supported by RCD Foundation, Mark Hughes Foundation, DDB Remedy, Roche and the Cancer Council of NSW

Scientific meetings

Funding was provided for the 3rd Collaborative Paediatric Cancer Research Day at The Hudson Institute, June 29th, 2016. This type of sponsorship fosters scientific exchange, providing an impetus for scientific progress towards better treatments for children with cancer.

PhD Scholarships

Funding for paediatric brain cancer in Australia is too low to drive the developments of new treatments. This low level of funding supports few researchers and fails to attract new scientists into this field. From this low base it is difficult to attract more funding, creating a ‘Catch 22’. This impasse is largely being met by philanthropic organisations, such as The Isabella and Marcus Fund, by providing seed funding to drive new research that would otherwise go unfunded.

In addressing the shortfall in scientists, the charity is providing PhD scholarships to graduate students to become the next generation of paediatric brain cancer scientists. Scholarships are named in memory of children who have died from DIPG. These scholarships are funded by the charity’s association with Upstream Foundation.

Advocacy

The Isabella and Marcus Fund is a member of a the 'Low Survival Cancers Alliance' committee, lead by the Cancer Council Victoria. The committee advocates for increased funding for the 10 cancers with 5 year survival rates below 30%. In Victoria, these cancers represent 20% of all cancer diagnoses but encompass 50% of cancer deaths.

The committee was established in March 2016, has been meeting regularly and will officially launch in 2017. In 2016 the Alliance engaged with the Victorian Health Minister, provided a submission to the Advisory board of the Medical Research Future Fund and contacted the Chair of newly formed Federal Senate Select Committee for low survial cancers in preparation for a formal submission early in 2017.

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