Blocking Inflammasome-induced Neuroinflammation in Parkinson’s Disease with a Potent, Orally Available Small Molecule

The research team at QLD University

Study Rationale:
Our brains are full of immune cells called microglia, which fight infections and clear the brain of toxic products. In Parkinson’s disease, these cells are constantly active, leading to brain inflammation that damages neurons (nerve cells). Evidence of this inflammation is found in the blood and brains of Parkinson’s patients. To fight this damage, we developed small molecules (suitable to be be taken as a pill) that get into the brain, where they stopped brain inflammation in pre-clinical models of the disease. We hope this treatment could halt or even reverse Parkinson’s progression.

There are many different possible causes of Parkinson’s involving age, genetics, diets and lifestyle. Whatever the cause, we think our immune system’s response to produce inflammation in the brain is a key factor that drives Parkinson’s disease, and small molecule drugs that can penetrate the brain and stop this inflammation may be able restore the health of our brain immune cells, so they can get back to ‘cleaning up’ brain toxins.

Study Design:
We have used a small molecule, known as MCC950, to show that blocking brain inflammation can stop Parkinson’s in all three models of the disease that we created. However, MCC950 has a short life in the body, so we will design and test new molecules that act the same way, but are more drug-like, last longer, and could be developed as a once-a-day pill to stop brain inflammation.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Labeled versions of the small molecule may be able to be used in diagnostic imaging to check for brain inflammation. An oral pill could be developed to stop brain inflammation. We hope to prevent Parkinson’s disease worsening, or if the drug can be given early enough, stop it happening all together.

Next Steps for Development:
We will use medicinal chemistry to design and make improved versions of the original small molecule, and test for any long-term side effects and safety issues. We aim to expose as much of the brain as possible to a once-a-day treatment, which will be a more manageable schedule than current Parkinson’s treatments. If we can achieve this, then we can start further work that leads to investigative new drug approval from the Food and Drug Administration then clinical safety trials in humans.

About Matthew Cooper

Prof. Matt Cooper completed his PhD in 1995 and then spent 13 years in the United Kingdom, first at the University of Cambridge, then nine years in start-ups and biotechnology companies. He returned to Australia in 2009 as a NHMRC Australia Fellow at the University of Queensland, where he is driving research and development of infectious and inflammatory disease diagnostics and therapeutics. He was founder and managing director of Cambridge Medical Innovations (part of Alere Inc.), CSO and co-founder of Akubio, and co-founder of Defensin Therapeutics. He has more than 190 scientific articles, two books and 22 patents, and has helped launch multiple medical technology products on the market today.