The Luminesce Alliance Innovation in Paediatric Precision Medicine Seed Funding Round has been a tremendous success. Fifty nine applications were received with a total funding request of just under $11 million. This was more than anticipated. With a total funding pool of just $1 million it was not possible to fund all projects. The successful seed funding applications were:

A self-amplifying theranostic for treatment of neuroblastoma, Professor Phillip Hogg, University of Sydney

This study aims to evaluate the therapeutic efficacy of ¹⁷⁷Lu-CDI in unprimed or cyclophosphamide-primed murine neuroblastoma tumours. It is hypothesise that ¹⁷⁷Lu-CDI will bind to dying/dead neuroblastoma tumour cells and deliver therapeutic radiation to viable, potentially more resistant tumour cells adjacent to the dying /dead cells, and in combination with sensitising chemotherapy will generate a self-amplifying cascade of neuroblastoma tumour cell kill.

 

Curing genetic metabolic liver disease by precise genomic and epigenomic editing, Professor Ian Alexander, Children’s Medical Research Institute

While individually rare, genetic metabolic liver diseases are collectively common, difficult to treat and carry high morbidity and mortality. This study hypothesise that precise genetic and epigenetic editing at the human Ornithine transcarbamylase deficiency (OTC) locus can be used to restore physiological OTC expression in male and female patient-derived primary human hepatocytes in vivo at clinically relevant efficiencies. One of its aims is to optimize the efficient delivery of genetic and epigenetic editing reagents to patient-derived OTC-deficient primary human hepatocytes in vivo using elite AAV capsid technology (AAV-LB12) in combination with lipid nanoparticle (LNP) technology.

 

Translating disease severity biomarkers into the clinic for Rett syndrome, Professor Wendy Gold, University of Sydney

Rett syndrome is a rare severe neurodevelopmental disorder caused by variants in the Methyl-CpG-binding protein 2 (MECP2) gene. It is the second most common form of intellectual impairment in females. One of the aims of the study is to determine whether serum levels of FGF21 and GDF15 are prognostic biomarkers of disease stage and severity in girls with Rett syndrome.

 

Precision medicine addressing a novel disease pathway to preserve sight in the retinal dystrophies, Professor Robyn Jamieson,  Children’s Medical Research Institute

Inherited Retinal Diseases (IRDs) affect approximately 1:1000 people or leads to an inexorable degeneration to blindness. There is marked genetic heterogeneity hampering individual gene therapeutic efforts. This project aims to develop a novel therapeutic approach towards a disease pathway we have recently identified, that will be applicable to the broad group of IRDs, thus able to benefit a large proportion of patients.

 

LA Centre for RNA Diagnostics: A pipeline of accredited RNA Diagnostics to extend diagnostic yield of rare disorders by 25 % in 5 years, Professor Sandra Cooper, Sydney Children’s Hospitals Network

Variants of Uncertain Significance (VUS) leaves families and clinicians with no actionable answer and health systems with no diagnostic return on their investment into genetic sequencing. This health implementation project will establish a centre for RNA Diagnostics that will provide an accredited RNA diagnostic service with 95% diagnostic return (ie 95% variant re-classification). It will aim to resolve pathogenicity of splicing variant VUS for 60 families with rare monogenic disorders or germline cancer.

 

The reviewers commented on the diversity received and the high calibre of the applications. It was very encouraging to see the breath of paediatric precision medicine research emerging from the Luminesce Alliance partners.