Become a mito research partner

Mito Multi Disciplinary Team towards a 70% Diagnostic Rate for Mito Patients by 2025

The Problem

For mito patients, the road towards a genetic diagnosis is often extremely long and arduous. The current diagnostic rate of patients is between 40-50% whilst the other 50-60% face a diagnostic odyssey. There are huge physical, psychological and financial ramifications for patients who live without a diagnosis. As well as the impact at the individual level, there are impacts at the public health, government and economic levels. Improved diagnosis of mito would lead to better health outcomes and less strain on the healthcare and economic system.

The Medical Research Future Fund Genomics Health Futures Mission released $3M in research funding in a targeted call to “identify and diagnose novel rare diseases and increase the genomic diagnostic rate towards 70% by 2025”. Reaching a milestone like a 70% diagnostic rate is no small feat for a disease as complex as mito. There are over 350+ genes that are known to cause mito, and many more mutations in these genes called ‘variants of uncertain significance’, meaning whether they cause mito or not is still unknown.

The recent passing of Maeve’s Law means Australian women carrying certain forms of mito will soon have access to mitochondrial donation, an IVF technique, to prevent passing mito onto their children. As with any effective treatment or prevention measure, its success hinges on people having a confirmed genetic diagnosis.

Currently, the main way to diagnose mito is through genomic sequencing of DNA. Genomic testing does not always find the responsible gene mutation for a patient’s disease. New ‘omics’ testing approaches such as transcriptomics, proteomics and metabolomics are needed to increase the number of patients being diagnosed.

“There are huge physical, psychological and financial ramifications for patients who live without a diagnosis.”

OUR SOLUTION

Combining these 4 omics approaches together, and undertaking targeted analyses of patient samples, requires a large, multidisciplinary team to tackle this complex task and achieve a 70% diagnostic rate within the next 3 years.

Dr David Thorburn is leading the first truly national consortium approach to improving the diagnosis of mitochondrial diseases using genomic and additional ‘omic’ approaches. This team includes researchers and diagnostic scientists from 6 laboratories in Victoria, NSW and Western Australia plus clinicians from around Australia. Not only will they improve the diagnostic rates of mito, but they will also demonstrate that the technological and organisational approaches they will develop can be effectively deployed for other rare diseases. Conditions with overlapping clinical presentations include epilepsy, neuropathy and spastic paraplegia. The team will define paths to incorporate omics into pathology testing, identify novel genes, mechanisms and phenotypes to enable personalised treatments to achieve better health outcomes for mito patients.

This project will seek to identify the genetic cause in over 200 undiagnosed mito patients, triaging patients who are unsolved after clinical genomic testing by testing them using the extended omics methods. The initiative is expected to confirm that many variants of uncertain significance are actually pathogenic and to identify novel causes in patients who currently lack any indication of a specific causative gene. This will widen the growing list of genes and mutations implicated in the disease to help diagnose more patients in the future.

“Not only will they improve the diagnostic rates of mito, but they will also demonstrate that the technological and organisational approaches they will develop can be effectively deployed for other rare diseases”

The Next Step

A team of over 18 researchers and clinicians, as well as Mito Foundation, has committed to the mitoMDT project to complete the first aim of the project by establishing this multi-disciplinary team. This network is identifying patients for diagnostic testing and co-ordinating advice nationally. Testing can begin after recruitment. Mito Foundation wishes to partner on this project set up by the Genomics Health Futures Mission to provide more than 200 patients with the opportunity to access this diagnostic program, and to emphasise the importance of this initiative.

To proceed, we seek funding to the value of $300,000 (or $100,00 per year over three years) to unlock $10,000 in further funding for every $1,000 invested by Mito Foundation to lift this project off the ground.
Every $10,000 can support full genomic and omic testing for 1 patient.
$300,000 from Mito Foundation will facilitate a total of $3 million from the Genomics Health Futures Mission.

The Outcome

The complexity of mito means families often wait many years for a genetic diagnosis, delaying the use of any specific therapies, if available, or the provision of accurate information about prognosis and recurrence risk.

This project could help end the diagnostic odyssey, avoid unnecessary investigations such as invasive tissue biopsies, restore reproductive confidence and as new treatments are developed, to have a cohort of clinical trials-ready patients documented in the Mito Foundation’s Mito Registry.