Pharmcological Targeting of the NLRP3 inflammasome

Shake It Up has committed to a research project at University of Queensland focused on inflammation.

To give you a better understanding of this research we sat down with the lead researcher in the study, Associate Professor Trent Woodruff to learn more about this important area of research.

Here is a summary of that discussion:

Project name:
Pharmacological targeting of the NLRP3 inflammasome in pre-clinical models of Parkinson’s Disease using potent orally active inhibitors.

Research team:
Our Parkinson’s research team is led by Associate Professor Trent Woodruff, and includes Dr Richard Gordon as the lead post-doctoral scientist driving the research. For this project we are also working with other researchers at UQ with specific areas of expertise in Immunology (Dr Kate Schroder), and Drug Development (Prof Matt Cooper).

What area of Parkinson’s are you researching?
Our major research focus is exploring the deleterious roles of the innate immune response and the chronic neuro-inflammation that occurs in the brains of patients with Parkinson’s Disease. We work closely with our collaborators both in Australia and internationally to identify, develop and test novel drugs to slow down or reduce this sustained neuro-inflammation in preclinical disease models.

Why is this research important?
There is accumulating evidence from patient studies and preclinical models which suggests that a chronically overactive immune response in Parkinson’s disease patients can accelerate the ongoing loss of the dopamine producing brain cells. This consequently drives the progression of Parkinson’s disease. Our aim is to therefore target this overactive immune response and the excessive neuro-inflammation in order to slow down or halt disease progression.

What are you trying to discover?
A better treatment for Parkinson’s disease, or a feasible means to significantly halt the progressive worsening of disease in patients.

Where is the research up to?
We have very exciting pre-clinical data in multiple models of Parkinson’s disease for our orally active drugs. Most significantly, we have recently confirmed that the pathway which our drug blocks, is over-activated in the brains of Parkinson’s disease patients. Further, we have now identified a novel mechanism by which this signalling pathway can drive Parkinson’s disease pathology and have confirmed that our current drugs are effective in blocking this pathological process.

Currently, we are working with our collaborators on developing next generation inhibitors of this pathway, which are capable of entering the brain at lower doses, and which would make for better drugs in the clinic. We are also moving towards testing our current drugs in non-human primate models of Parkinson’s disease, which is the next major step in the drug development process for Parkinson’s.

What drives your commitment to find better treatments for Parkinson’s?
We are driven by our research findings, which are pointing more and more to a role for the immune system in Parkinson’s disease burden. We are very fortunate to collaborate with medicinal chemists who are developing novel drugs to block these pathological immune cascades in the brain. Our findings in animal models of Parkinson’s disease, indicate that these drugs can limit inflammation in the brain, and reduce dopamine neuron loss, and therefore reduce disease symptoms. Our hope for the future is to take these novel drugs into human clinical trials for Parkinson’s treatment. This is what drives us to turn up to work each day – the anticipation to one day identify a treatment that can greatly slow disease in Parkinson’s sufferers.