MND drug nears clinical trials
For researchers investigating desperately needed treatments for motor neurone disease, moving laboratory discoveries through to clinical trials can seem an interminable process.
This is the time they refer to as the ‘valley of death’, as many promising drug candidates are left languishing in its metaphorical depths for want of financial backing. Seeing it through to patient trials requires resilience, patience and often a fair smattering of luck.
For UQ alumnus Associate Professor Trent Woodruff, and a drug codenamed ‘PMX205’, the end of the pipeline is in sight. PMX205 is an inflammation-inhibiting drug that has the potential to improve outcomes for MND patients by slowing the progression of the disease and managing symptoms.
Dr Trent Woodruff
The project began in 2008 with Dr Woodruff’s NHMRC Career Development Fellowship, and expanded when he started his own research group at UQ’s School of Biomedical Sciences two years later.
“We’d been plodding along with our investigations. Then the Ice Bucket Challenge went viral and some high-profile cases created some much-needed momentum.
“Since then we’ve been fortunate to obtain the backing of a private drug company, along with funding from FightMND and Advance Queensland. As part of the Advance Queensland grant, we’ve also attracted funding from Huntington’s Queensland and the MND and Me Foundation,” Dr Woodruff recalls.
This support has led to rapid acceleration of the research towards human trials. Earlier this year, Dr Woodruff’s team had expected that the earliest the first patients would trial the drug would be 2019. Now that may be as early as next year, assuming the drug is shown to be safe in preclinical testing.
Any prospective clinical trial cannot come soon enough for the hundreds of Australians diagnosed with MND each year. As researcher Dr John Lee explains, there is no known cure and the average life expectancy is only two and a half years.
Dr Woodruff and Dr Lee in the lab
“Currently the only drug available for patients prolongs survival by two to three months at most,” says Dr Lee.
“In animal models, PMX205 made a visible difference to tremors, muscle strength and mobility. If this is reflected in people, it could make a real difference to patients.”
Dr Lee completed his PhD in the Woodruff Laboratory, and is now an MND Research Institute of Australia Postdoctoral Fellow.
Since the FightMND funding, the drug company sponsor has scaled-up manufacture of PMX205 and undertaken formal preclinical trials. The toxicology results, together with research already published, will be presented to the US Food and Drug Administration for approval to begin administering the investigative drug in humans.
Team member Raquel McGill takes a blood sample to identify MND markers.
In the meantime, as Dr Woodruff explains, the School of Biomedical Sciences is testing the drug in a range of motor neurone disease models.
“Our initial experiments involved the inherited form of MND, but we believe the same inflammatory pathway is likely to be active in all forms of MND. Our next project will focus on sporadic MND, which accounts for 90 per cent of patients.”
Dr Woodruff’s team is also identifying biomarkers in blood samples collected from patients at a Brisbane MND clinic.
“We are still investigating how the drug affects molecular processes to delay MND symptoms and extend survival,” the researcher says.
Dr Woodruff supervises an experiment
Dr Woodruff recounts the time during his student days when his fascination with the way drugs worked was piqued.
“I was in the second year of an undergraduate degree in science, and I asked my pharmacology lecturer how paracetamol worked. I’d suffered from headaches when I was younger, and taken quite a bit of it, so I was intrigued when his answer was that no one really knew.
“Researchers are yet to fully answer that question, and I often share the anecdote with my students in the hope that it will spark their curiosity too.”
This story is featured in the Summer 2017 edition of UQMedicine Magazine. View the latest edition here. Or to listen, watch, or read more stories from UQ’s Faculty of Medicine visit our content hub, MayneStream.