Grants to improve diagnosis of rare diseases

Five Murdoch Children's Research Institute (MCRI) researchers have received funding for studies that aim to increase rare disease diagnoses and improve patient outcomes.

Professors Andrew Sinclair, John Christodoulou, Paul Lockhart, David Thorburn and Zornitza Stark have secured funding to advance Australia's genomics research from the Medical Research Future Fund (MRFF). The funding is part of the 2021 MRFF Genomics Health Futures Mission round, announced by Federal Health Minister Greg Hunt.

Despite the enormous progress in genomic sequencing, nearly half of all people with a rare disease do not receive a genetic diagnosis. Limited knowledge of the underlying pathology of the thousands of rare diseases hinders the ability to develop potential treatments.

In order to address this enormous and growing unmet need, a national consortium co-led by Professor Sinclair (MCRI) and Professor Sally Dunwoodie (Victor Chang Cardiac Research Institute) established the Australian Functional Genomics Network (AFGN).

"The $6 million from the MRFF will allow us to harness the resources of over 200 model organism researchers across Australia to increase our understanding of the gene variants that may cause disease. This will lead to improved diagnostic rates, but also provide insights into effective treatment options," he said.

Professor Christodoulou's project aims to increase the rate of rare disease diagnosis to over 70 per cent within three years, which will drastically shorten the diagnostic odyssey for people living with 'orphan disorders.'

"Despite the creation of new gene sequencing technologies, half of the people with rare genetic disorders remain without a diagnosis. To address this gap we will establish the Undiagnosed Diseases Network of Australia, bringing together a national crack team of medical specialists, diagnostic laboratories, computing experts and researchers," he said.

Professor Christodoulou said the national network, which includes researchers from every state and territory in Australia, will harness the latest genomic technologies, emerging computer-based tools and lab-based techniques to boost the diagnosis in these unsolved cases.

Professor Lockhart's project will focus on neurogenetic disorders including ataxia, a degenerative disease of the nervous system which causes slurred speech, trouble eating and swallowing, and difficulty walking, with patients often requiring wheelchairs or walkers to aid their mobility.

"Identifying the genetic cause of disease in an individual is often the first step in the provision of appropriate clinical care. This diagnostic process is being revolutionised by our ability to sequence the entire human genome in a time and cost-effective manner," he said.

Professor Lockhart said this important study, being undertaken in collaboration with Professor Bahlo and Dr Rafehi at the Walter Eliza Hall Institute, would develop a tool to provide rapid diagnoses and better clinical care for individuals with neurogenetic disorders.

Professor Thorburn's project focuses on mitochondrial disease, the most common group of inherited metabolic disorders, which can be caused by changes in more than 350 different genes and affect any or all of our organ systems.

"New genomic (DNA) technologies have increased our ability to diagnose mitochondrial diseases from less than a quarter of patients to about a half," he said. "Our project establishes a national network seeking to identify new genes, mechanisms and phenotypes while enabling personalised treatments and achieving better health outcomes for patients with these diseases."

The study seeks to further improve the diagnostic rate by using new '-omic' technologies, that can simultaneously detect changes in thousands of proteins and molecules.

Professor Stark, clinical geneticist at the Victorian Clinical Genetics Service and Clinical Research Fellow at Australian Genomics, will lead a national program to increase the rate of diagnosis for patients who have undergone genomic testing by harnessing the power of existing genomic data.

"Re-analysing existing genomic data over time significantly improves diagnosis in rare disease. Despite strong support at professional and health policy levels, routine reanalysis is currently limited by a heavily manual process. We will unlock the potential for data to provide answers to families through large-scale automation of the reanalysis process," she said.

Professor Stark's team will develop, implement, and evaluate a national program for automating and scaling up the reanalysis process, which is expected to benefit thousands of families affected by rare disease. This project is led by a national team including Dr Daniel MacArthur, Director of the Centre for Population Genomics a new partnership between MCRI and the Garvan Institute of Medical Research.