An egg with mito in red, mtDNA in green and nuclear DNA in blue (C) Dr Inwon Lee
Around 50 Australian children are born every year with devastating mitochondrial disease (mito), with an expected lifespan of only five years. The Medical Research Future Fund has announced $15 million in funding to an Australian first – and only the second in the world – clinical trial of mitochondrial donation. This technique provides hope to Australian families affected by mito and has the potential to prevent children from being born with mitochondrial disease.
Mitochondrial DNA is inherited via the mother’s egg and is responsible for helping mitochondria to generate energy in all the body’s cells. If mitochondrial DNA carries variants that lead to faulty energy production, this can cause mitochondrial disease. Mitochondrial donation aims to correct this genetic timebomb through a form of assisted reproductive technology in which the future baby’s mitochondrial DNA comes from a donor egg, to avoid passing on inherited mitochondrial diseases.
Mitochondrial disease (mito) is a debilitating, potentially fatal genetic disorder that robs the body’s cells of the energy they need to function properly. Mito can have a devastating effect on families, including the premature death of children, painful debilitating and disabling suffering, long-term ill health, childhood dementia and poor quality of life.
More often than not, mito is caused by a change in the mitochondrial DNA, which is passed down the maternal line, rather than by changes in regular nuclear genes. Mitochondrial donation is an IVF-based technique that allows women with mitochondrial DNA disease to have children without passing on their faulty mitochondrial gene. The technique involves removing the nuclear DNA from a patient’s egg containing faulty mitochondria and inserting it into a healthy donor egg, which has had its nuclear DNA removed.
The mitoHOPE (Healthy Outcomes Pilot and Evaluation) Program, includes mitochondrial and clinical geneticists at Murdoch Children’s Research Institute and around the country, fertility specialists and clinical embryologists from Monash IVF working together with reproductive scientists from Monash University and the University of Adelaide. The team also includes Monash clinical trial experts and a team of social science researchers to engage with the community. The consortium is led by Professor John Carroll, Director of the Monash Biomedicine Discovery Institute (BDI) and an expert in mitochondrial activity in egg and embryo development.
“The entire mitoHOPE team is committed to making this a success for all families who have mitochondrial genetic disease. The Mito Foundation first introduced me to families who have experienced this devastating disease, often over generations, and ever since it has been a priority to ensure we can deliver mitochondrial donation in Australia,” Professor Carroll said.
This trial – based in Melbourne in collaboration with Monash IVF, will be available to eligible women from all over the country. Professor John Christodoulou who with Professor David Thorburn of the Murdoch Children’s Research Institute will lead recruitment into the clinical trial said, “we have ensured a national network of clinical geneticists is available to facilitate entry to the trial, and the national presence of Monash IVF further enhances this.”
Monash IVF Group Medical Director, Professor Luk Rombauts, said the five-year project would allow eligible women across Australia to use assisted reproductive technology to improve their chances of having healthy children.
“By introducing mitochondrial donation in the clinical IVF laboratory, we can prevent some children from suffering from this life-threatening disease and reduce the burden of mitochondrial disease on families and our health system,” Professor Rombauts said.
Monash IVF Group Chief Scientific Officer, Associate Professor Deirdre Zander-Fox, added:
“Mitochondrial donation cannot cure people with existing mitochondrial disease or prevent mitochondrial disease caused by mutations in an individual’s nuclear DNA, but it can help minimise the risk of a child inheriting mitochondrial disease from their mother with the help of IVF.”
Importantly, an intensive research program will be based at the Monash University BDI laboratories, with coordinated research activities at Monash IVF clinic, with national partners including Professor Rebecca Robker at the University of Adelaide and the BDI, and ongoing research at Newcastle University in the UK. This unique research capability will build on the knowledge base established at Newcastle University and ensure the development of the most effective new technologies.
Building on a long-standing partnership between Monash University and Newcastle University (UK) where the world’s first mitochondrial donation program is being offered, the mitoHOPE program brings together expertise and experience from both centres that will ensure the best possible start to the program.
Professor Mary Herbert, a pioneer of mitochondrial donation, who will move to Monash in March 2023 said “Our team is uniquely placed to optimise and translate MD technology into an Australian clinical trial setting. Concurrently, we will build a knowledge base to improve the efficacy of mitochondrial donation, monitor safety and establish the feasibility of wider implementation,” Professor Herbert said.
According to Sean Murray, CEO of the Mito Foundation, if successful, “the mitoHOPE Program will allow members of the Australian mito community to have their own biological children free from mito,” he said. “For some families, this will end generations of devastation from the impacts of mito. The mitoHOPE Program is a beacon of hope for the Australian mito community.”
“Monash University has been a pioneer and world leader in IVF technology and mitochondrial research for over four decades. This trial represents Monash University’s strength in this field and our ongoing commitment to advancing this important work,” said Pro Vice-Chancellor (Research), Professor Mike Ryan, who also heads the Mitochondrial Biology and Disease Laboratory at Monash and is a Director at the Mito Foundation.
Professor Catherine Mills, from the Monash Bioethics Centre, working closely with the Mito Foundation, will ensure the mitochondrial disease community is engaged in all aspects of developing the trial. “This will underpin best practice care to ensure the psychosocial wellbeing of participants and their families, minimise the burden of participation, and enable equitable and ethical operation of the trial,” Professor Mills said.
The success of the MitoHope program will depend on the willingness of Australian women to donate eggs for reproductive purposes and for use in research to improve the technical procedures. “We will be calling on women to consider egg donation for this incredibly important cause”, said Professor Mills who in collaboration with Monash IVF will coordinate the egg donor recruitment programme.
Enabling at-risk women to access mitochondrial donation will not only stop the inheritance of mitochondrial genetic disease across generations but also create savings in future healthcare costs of $500 M AUD over 10 years, according to UK health economic studies’ predictions.
