Children’s Medical Research Institute (CMRI) was awarded multiple Medical Research Future Fund (MRFF) grants to help improve the lives of children living with genetic diseases. The MRFF, which is an initiative of the Australian Government, has funded research projects in cancer, gene therapy, and stem cell medicine at CMRI.
Dr Anai Gonzalez-Cordero, head of the Stem Cell and Organoid Facility and Stem Cell Medicine Group at CMRI, has been awarded the MRFF Stem Cell Therapies Grant to investigate new gene therapies for inherited eye disease.
Dr Gonzalez-Cordero and her team, in collaboration with A/Prof Leszek Lisowski and Prof Robyn Jamieson, Prof Ian Alexander, and Prof John Grigg (of SCHN and CMRI), as well as Dr Carvalho at the Lei Institute in WA, will collect induced pluripotent stem cells (iPSC) from patients’ own cells to generate mini-organs (3-dimensional organoids), specifically of the retina. Thanks to the $498,000 award from the MRFF, Dr Gonzalez-Cordero will be able to test new gene therapies on these retinal organoids and try to reverse the blinding effects of inherited eye disease.
A key tool in gene therapies is the use of adeno-associated virus (AAV) vectors. Where Dr Gonzalez-Cordero will use an AAV vector to treat blindness, Associate Professor Leszek Lisowski, head of the Vector and Genome Engineering Facility and Translational Vectorology Unit at CMRI, will attempt to treat Friedreich’s Ataxia, a genetic disease that causes progressive nervous system damage and movement problems.
A problem with the AAV vector is its difficulty in targeting neuronal and cardiac cells, making them ineffective in the treatment of neurological diseases like Friedreich’s Ataxia. A/Prof Lisowski, in collaboration with Associate Professor Mirella Dottori from the University of Wollongong, was awarded $983,000 to address this major roadblock and develop superior AAV vectors (called ‘SMART AAVs’) that specifically target human cardiac cells, sensory neurons and cerebellar neurons.
Professor Hilda Pickett and her team have long investigated telomeres, the short DNA stretches located at the ends of chromosomes that are important to cancer and aging. Unlike normal cells, where telomeres shorten every time a cell divides, the telomeres in cancer cells maintain their lengths, enabling them to keep growing. There are two methods cancer cells use to achieve this: telomerase and the Alternative Lengthening of Telomeres (ALT) mechanism.
Osteosarcoma is the most common type of primary bone malignancy, with the highest incidence in adolescence. The ALT mechanism is used by nearly 60% of osteosarcomas, yet no ALT-specific treatment strategies currently exist. Courtesy of a $1.48 million grant, Prof Pickett and her collaborators on this project (Prof Roger Reddel and A/Prof Tony Cesare of CMRI) can exploit a newly found Achilles’ heel of ALT cells to create chemical inhibitors toxic to ALT cells, improving treatments for adolescent osteosarcomas.
The Australian Government has contributed $2,961,000 in total to research at CMRI through these MRFF grants, and their support is a huge step towards beating children’s genetic diseases.
Learn more about the MRFF at http://www.health.gov.au/mrff