Parkinson’s and inflammation

Inflammation is essential for protection and recovery in the short-term, but prolonged inflammation, especially in the brain, is thought to contribute to Parkinson’s progression.

What is inflammation?

Inflammation is the body’s natural response to injury, infection or damage. It is driven by the immune system and is aimed at protecting and healing cells and tissues. This process is usually harmless, subsiding once a threat is dealt with; however, prolonged inflammation can cause issues as immune cells may begin to target and damage nearby healthy cells.

Outside the brain, immune cells called macrophages and neutrophils work together to fight infections. However, the brain is protected by the blood-brain barrier (BBB), which shields it from harmful substances. Because of this, the brain relies on its own immune cells, primarily microglia and astrocytes. Microglia, a type of macrophage, act as the brain’s primary defence by responding to signals of injury or distress and initiating an immune response.

How is inflammation relevant to Parkinson’s?

There is growing evidence to suggest that prolonged inflammation in the brain, called neuroinflammation, is common in people with Parkinson’s and may contribute to Parkinson’s progression through several pathways.

In Parkinson’s, one of the critical mechanisms of neuroinflammation involves microglia. These cells are found in high concentrations in the substantia nigra, a region of the brain where we see the most neuron loss in Parkinson’s. When microglia detect signals of neuron damage or stress, they become activated, releasing pro-inflammatory signalling molecules. This immune response, though protective in the short-term, can become detrimental over time as prolonged inflammation damages nearby healthy neurons.

One key process in microglial activation is the activation of the NLRP3 inflammasome. Inflammasomes are complexes of multiple proteins which assemble and initiate inflammation during an immune response. Abnormal alpha-synuclein, a protein associated with Parkinson’s, is believed to activate the NLRP3 inflammasome, further exacerbating inflammation and potentially accelerating neuron damage.

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Reducing inflammation to slow the progression of Parkinson’s

Researchers have been investigating whether reducing inflammation in the brain can help slow down the progression of Parkinson’s.

Cure Parkinson’s and Van Andel Institute are currently funding a Phase 2 clinical trial of dapansutrile, an anti-inflammatory drug that reduces the activation of the NLRP3 inflammasome. Dr Caroline Williams-Gray from the University of Cambridge is leading the trial which will involve 36 people with Parkinson’s, who will be treated with dapansutrile tablets for up to 12 months. The results of this trial will be used to help determine whether dapansutrile should be evaluated in a larger, phase 3 clinical trial as a potential disease-modifying treatment for Parkinson’s.