Study Rationale:
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.
Hypothesis:
Brain imaging of inflammasomes in immune cells can help identify Parkinson’s patients and tell us if new therapies that inhibit neuroinflammation are working
Study Design:
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.