Chronic inflammation of immune cells our brains is now believed to be associated with the onset and progression of Parkinson’s disease. These cells produce a target in Parkinson’s patients called the NLRP3 inflammasome, which is validated as a key driver of neuroinflammation. Inflazome has developed a clinical candidate drug that blocks this target and that may stop the chronic cycle of inflammation and damage to neurons. This project aims to develop an imaging probe to non-invasively image the brain and report how much NLRP3 is present. This diagnostic may help diagnose early onset disease, and will also support the first trials in Parkinson’s patients.
Brain imaging of inflammasomes in immune cells can help identify Parkinson’s patients and tell us if new therapies that inhibit neuroinflammation are working
We will prepare compounds that incorporate labels that can be imaged with a PET scanner. We will test how these compounds bind to post-mortem brain slices from people with Parkinson’s disease and conduct imaging studies in pre-clinical models with Parkinson’s-like symptoms. We will also examine how much of the PET tracer gets into the brain, how specific its binding is and how long it lasts.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This diagnostic will allow clinicians to see how much NLRP3 neuroinflammation is present in the patient’s brain. It can be used to investigate the role of NLRP3-driven inflammation in the development of Parkinson’s disease and to work out dosing of NLRP3-targeting drugs. The tracer may also be useful in other NLRP3-associated diseases such as Alzheimer’s, motor neuron disease, and multiple system atrophy.
Next Steps for Development:
Once the PET tracer has been developed, next steps will be testing it in human volunteers.