Taking the path less travelled to stop brain diseases in their tracks

By Michelle Schlechta

Credit: Andrew Care

Tiny structures called nanocages have the potential to revolutionise treatment of conditions like Parkinson’s and Alzheimer’s diseases.

Two researchers, seemingly worlds apart: one a nanoscientist, the other a neuroscientist. Born in different hemispheres with labs in different states, at the start of their game-changing collaboration 2 years ago, they felt they were speaking different languages.

‘I remember the first few meetings,’ laughs Assoc Prof Lyndsey Collins-Praino, from the University of Adelaide. ‘We would just draw things on a piece of paper, hold it up to the camera and say, “Look! This is what I’m talking about!”’

Yet her partnership with Dr Andrew Care from Macquarie University in NSW and their audacious science may lead to a breakthrough treatment for one of the most insidious and heartbreaking disease groups: neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease, which devastate millions of lives.

The common denominator in their story is the Centre for Nanoscale BioPhotonics (CNBP) and its innovative director, Prof Mark Hutchinson. Both researchers are associate investigators with the CNBP; Dr Care works with nanoparticles called ‘protein nanocages’ and Assoc Prof Collins-Praino is interested in how disease spreads through the brain in neurodegenerative disorders and, more importantly, how to stop it.

Knowing the strength of each scientist’s work, Prof Hutchinson wondered what they might achieve working together.

Could nanocages — tiny structures able to infiltrate cells — be used to disrupt rogue protein clumps that seem to be the culprits in such disorders as Parkinson’s and Alzheimer’s? If so, they might stop disease in its tracks.

‘Mark’s a real ideas man. I knew nothing about neurodegenerative disease, but he put me in touch with Lyndsey and the rest is history,’ says Dr Care.

Credit: PopTika / Shutterstock

Assoc Prof Collins-Praino is a translational neuroscientist from Pennsylvania, who moved to Adelaide 6 years ago. ‘Pretty much since I was 16, I’ve wanted to be a neuroscientist,’ she explains. ‘I had a family member get quite ill with a neurological disorder and one thing that astounded me at the time was how limited treatments were, so I wanted to dedicate my career to trying to make sure that no-one had to hear that there weren’t any treatment options.’

Dr Care’s story is ‘a bit less focused, a bit more stumbling’, and has taken him from trying to solve climate change to working on a cure for Parkinson’s disease. He left his native New Zealand to do a PhD in Australia in 2011. A synthetic biologist, he began engineering enzymes to produce biofuels before shifting focus to biomedicine where he now engineers proteins to guide therapeutic drugs.

Dr Care initially tried to use inorganic nanoparticles to target drugs,  but found them frustratingly inflexible, so he looked to nature’s proteins to solve these problems. Here, he found ‘protein nanocages’ – tiny nanoparticles that are produced naturally inside bacterial cells. Using genetic engineering, these nanocages can isolated and modified to carry drugs, and there is promise that they will seed a new generation ‘targeted delivery vehicles’ for precision chemotherapy.

Dr Care was applying nanocage technologies to cancer when Prof Hutchinson suggested he and Assoc Prof Collins-Praino discuss whether they could disrupt the spread of the tangled proteins that sweep through the brain in neurodegenerative disorders, leaving disease and devastation in their wake. It was a powerful new idea for early intervention; ‘pie in the sky,’ says Assoc Prof Collins-Praino, but with legitimate potential.

‘I think when you look at neurological diseases in general, but neurodegenerative diseases in particular, new treatments really are small steps on old treatments, and a lot of that has to do with the challenges inherent in dealing with the brain,’ says Assoc Prof Collins-Praino. ‘We looked at what was happening and went, “Nope, we’re going to do something totally different”.’

As a researcher who’s in touch with vulnerable patients day after day, Assoc Prof Collins-Praino is naturally cautious about over-stating the potential of the work. For people living with a neurodegenerative condition, hope is good, but false hope is cruel. She and Dr Care have had success with cellular models and their mechanism is well-grounded in science, but they know there’s a long way to go. Looking for the commonality in disease mechanisms will, she believes, drive change.