Dr Jeffrey Liddell from the University of Melbourne is a mid-career neurobiologist, with an interest in neurodegenerative diseases and understanding their underlying causes.
'My primary motivation is my love of science. I love the process of posing questions and designing and running experiments to answer those questions,' said Dr Liddell.
'But research needs to be pragmatic and seek to address questions with serious health implications.'
This story is part of our 10 of the Best - thirteenth edition. 10 of the Best is an annual NHMRC publication, showcasing 10 NHMRC-funded health and medical research projects. See more 10 of the Best.
Dr Liddell's expertise is in glial cell biology, examining how these normally supportive cells in the brain can contribute to neurodegeneration and how they can be therapeutically targeted to either bolster their beneficial mechanisms or impede their pathological toxicity.
Dr Liddell joined an interdisciplinary research program at an incredibly exciting stage, when one of the lead compounds in development, CuII(atsm), showed strong benefits in animal models of multiple neurodegenerative diseases. The team had an effective drug but did not know how it worked.
'For Parkinson's disease, Alzheimer's disease and motor neurone disease, the causes are not known. The fact that we have a drug that is effective in animal models of these diseases gives us the very real possibility to uncover key mechanisms driving these diseases. The more we can learn about the drug CuII(atsm), the more we can learn about causes of these diseases,' said Dr Liddell.
The most relevant disease context of this research is motor neurone disease (MND). The average life expectancy after diagnosis of MND is 2.5 years and the total cost of MND to Australia in 2015 was $2.37 billion.1 Prevalence and mortality rates of motor neurone disease in Australia have approximately doubled in the last 3 decades.2
Dr Liddell was awarded the NHMRC Early Career Fellowship to research the mechanism of action of CuII(atsm) and the impact it had on specific cell types in the brain. The team found that CuII(atsm) preferentially releases its bound copper in disease-affected regions of the brain and exerts distinct protective effects when copper is bound or unbound
'I was lucky that NHMRC funding came along and highly supported our research,' said Dr Liddell.
The research has since demonstrated that CuII(atsm) exhibits strong efficacy in animal models of Parkinson's disease, stroke, sepsis and MND, which spearheaded the rationale to drive CuII(atsm) through to clinical assessment. Phase I clinical trials with MND and Parkinson's disease patients both generated very promising effects, and Phase II/III trials in motor neurone disease patients have recently concluded.
'Passing phase I trials mean that the drug should be safe for human administration. Surprisingly these small trials also produced encouraging results for the efficacy of the drug.
'These translational outcomes are the best possible result for a basic science research team.
'My advice for any early-career researcher is that they follow their passion. I love doing research, but it is hard work and if you are not driven internally, it won't be fun,' Dr Liddell said.
Next steps
Dr Liddell said, 'It is incredibly fulfilling to see that our research is now translating to the clinic, with the potential to make tangible and significant impacts upon the lives of people afflicted with serious diseases and their families.'
So far, there are no effective treatments for MND. Dr Liddell's team is actively investigating other neurodegenerative conditions, which may share underlying causes and be treatable with CuII(atsm).
CIA
Dr Jeffrey Liddell
Institution
University of Melbourne
Title
Metal complexes for the treatment of age-related diseases of the brain
Team members
Associate Professor Peter Crouch
Associate Professor Anthony White
Professor Paul Donnelly
Associate Professor Katja Kanninen
Dr James Hilton
Dr Kai Kysenius
Professor Ashley Bush
Grant information
$353,378
2013-2017
Early Career Fellowship
See also 10 of the Best
1 Deloitte Access Economics 'Economic analysis of motor neurone disease in Australia. A report for Motor Neurone Disease Australia'e Access Economics, 2015, Canberra.
2 Ibid.