Blood-based fingerprints of neuroinflammation in people with PSP and CBD

Pipeline Grant

Principal Investigator: Dr.  Maura Malpetti, University of Cambridge

Progressive Supranuclear Palsy (PSP) and corticobasal degeneration (CBD) are closely related brain diseases leading to changes in personality, communication and movement. Effective treatments to slow the disease are urgently needed. PSP and CBD cause early death of brain cells and brain shrinkage, together with a build-up of harmful junk protein. However, we have also discovered that there is chronic inflammation of the brain, and this starts long before people get symptoms. The more brain inflammation, the more severe the symptoms and the faster people decline. Treatments that target the brain’s immune system might therefore slow or prevent progression. This means that we need better tests to measure inflammation, to identify who will benefit most from treatment, when to treat them, and which part of the immune system to target.

Our overarching aim is to accelerate new treatments for PSP and CBD. In this study, we will improve the characterisation and clinical utility of innovative blood tests that measure specific patterns of inflammation in people living with these conditions. We call these patterns “fingerprints” and link the blood test changes to the brain inflammation. We introduce a new technology into the PSP/CBD field, called mass cytometry, alongside our existing methods to define the “fingerprint” of chemicals and cells of the immune system in people with PSP and CBD. Such blood tests have the advantage of being scalable, accessible, and mechanistically relevant. This will reduce the time, risk, and costs of new clinical trials. We focus on blood tests as they would be easier to access and use than other specialist tests for larger numbers of people affected by PSP or CBD. These tools may be key to forecasting clinical progression and identifying the targets upon which effective treatments can be developed – similar to the successful medical approach to blood pressure and cholesterol as modifiable targets for the prevention of stroke and heart disease.