Dr Marguerite Evans-Galea

Murdoch Childrens Research Institute


Brief description of your research (i.e. what disease are you hoping to treat/cure?)

Friedreich ataxia is a progressive, degenerative disease that affects the nervous system, especially the spinal cord and the brain, causing a wide-range of symptoms that get worse over time. It is the most common inherited ataxia and usually begins in childhood around age 10. Individuals with Friedreich ataxia become increasingly unsteady, lose coordination, and ultimately require a wheelchair. They also experience speech and hearing impairments, skeletal deformities and muscle weakness, yet their intellectual ability is not affected. Friedreich ataxia markedly shortens lifespan due to severe heart disease (cardiomyopathy and/or arrhythmia) and on average individuals die around age 40.

Friedreich ataxia affects 1 in 29,000 individuals and there are more than 300 families in Australia currently living with this disease, and several families have more than one affected member. Disease is caused by an alteration in a gene called FXN which instructs cells to make frataxin protein. There are lower levels of frataxin in people with Friedreich ataxia compared to unaffected individuals, and this particularly affects cells in the nervous system and the heart. Therapeutic strategies aim to increase frataxin.

My team is developing novel therapies for Friedreich ataxia using disease models in the laboratory. Introducing a healthy copy of FXN can increase frataxin and improve disease symptoms in mice with Friedreich ataxia. We deliver this healthy copy using bone marrow cells. “Corrected” mice have higher levels of frataxin in their spinal cord and importantly, mice that receive bone marrow cells perform better at tasks testing coordination and locomoter activity. This could mean the difference between needing a walker versus a wheelchair for individuals with Friedreich ataxia. We are now developing gene therapy ‘vectors’, which are inactivated viruses engineered to act like a Trojan horse and deliver frataxin into cells. Our proof-of-principle data provide compelling new evidence that cell and gene therapies have the potential to improve Friedreich ataxia.

Where are you hoping your research will take you?

The primary goal of my collaborative research program is to help people living with serious neurodegenerative disease. To do this, I am developing an internationally recognised translational research program that investigates inherited neurogenetic diseases to inform the development of novel therapies. I want to go all the way in my research career – I always have. I want to be here in another 20 years having translated our discoveries to the clinic.

Our research is ready to go to ‘the next level’. Purposeful change in my research training and experience has provided me the requisite expertise and international professional network to achieve my goals. I am also doing an internship with the MCRI’s business development team and actively seeking collaborative industry partners to facilitate broader application and translation of our cell and gene therapy program in Australia.

I also actively support and mentor the next generation of scientists, particularly women in science. I engage regularly with young researchers, present at their workshops and mentor students and researchers at different stages of their careers. I’m also passionate about sharing my research broadly and have developed a strong public profile, regularly communicating via social and national media. Understanding disease mechanism and developing cell and gene therapy is an exciting challenge, particularly in neurodegenerative diseases like Friedreich ataxia. I’m keen to see our research program expand and help more people!

What do you need, as a female scientist, to keep doing your research?

 When a new Group Leader begins their independent research career in the US, they receive a 5 year 'start-up package'. This has the usual trimmings of space, salary and funds for research and equipment, but just as importantly, it also has a suite of professional development and leadership opportunities, as well as administrative support. This provides a young woman researcher in the US, an outstanding foundation on which to build a successful career. A champion or sponsor, and access to a broad multi-disciplinary professional network, is equally important.

In Australia, organisations struggle to provide such strong foundations. Women researchers instead often rotate for years on 12 month contracts, even when they have grants, making it difficult to plan their research long term, develop ongoing collaborations, successfully navigate career interruptions, and establish themselves as an independent researcher.

I have established international collaborations with leading researchers in cell and gene therapy and Friedreich ataxia in the USA, the UK and in Europe. I have an extensive professional network across academia, industry, education, business and government. My research has won several awards and I am recognised internationally for my work to understand disease mechanism and develop novel cell and gene therapies for the neurodegenerative disease Friedreich ataxia. As an executive member of the Australasian Gene and Cell Therapy Society, I work to strengthen cell and gene therapy research in Australia. The Society is expanding its network across the Asia-Pacific – this presents immense opportunities for accelerating personalised medicine and extending Australia’s research capacity.

Yet I am at the classic 'squeeze point' in the academic research career. To successfully continue in research and achieve my research goals, I need a stronger foundation on which to continue building a successful career that provides me the greatest opportunity to 'start-up' … and then fly!