Dr. Williams-Gray is a Rosetrees Trust-funded researcher based at the University of Cambridge, who is leading a team that is currently investigating the role of Toll-like receptors in brain inflammation and disease progression in Parkinson’s disease and its associated dementia. The team are using human post-mortem tissue from patients with Parkinson’s to explore the relationship between pathological changes and clinical course of the disease. In addition, they are using a novel laboratory-based model of Parkinson’s disease which will allow them to determine how Toll-like receptor blocking drugs will affect the inflammatory response and consequent nerve cell damage.
A recent review of Toll-like receptors in Parkinson’s disease and alpha-synucleinopathies, published by Dr. Caroline Williams-Gray and her team, supports the idea that these receptors may have potential as therapeutic targets. In their review, they have highlighted that there is increased interest in using treatments aimed at either preventing or stopping brain inflammation in these diseases.
“Toll-like receptors are critical for the activation of immune cells and inflammation in the brain – and evidence that they play a role in Parkinson’s disease is accumulating.” – Antonina Kouli (Postdoctoral Research Associate, University of Cambridge)
Dr. Williams-Gray’s group also studies immune activation and inflammation in the blood in Parkinson’s disease patients. This work has implicated changes in immune cell types and function in Parkinson’s (Williams-Gray et al., 2018; Wijeyekoon et al., 2018; Scott et al., 2018), and has shown that patients who have more inflammation in the blood when they are diagnosed have more rapid progression of their disease (Williams-Gray et al., 2016). Their work to date on human post-mortem tissue confirms brain inflammation and specifically implicates Toll-like receptors in Parkinson’s disease and these findings will enhance our understanding of the neuropathological basis of Parkinson’s disease dementia, once published. Work is ongoing on the laboratory model, and due to complete in the next few months. If successful, this may pave the way for clinical trials of Toll-like receptor blocking drugs for use in the treatment of Parkinson’s disease.
“There is an urgent need to develop treatments that can halt or slow down the progression of Parkinson’s disease, as well as other neurodegenerative conditions which cause dementia. Suppressing brain inflammation is an exciting potential strategy which may be relevant to many of these diseases, and Toll-like receptors may provide a specific therapeutic target.” – Caroline Williams-Gray (Senior Clinical Research Associate, University of Cambridge & Honorary Consultant Neurologist, Cambridge University Hospitals NHS Foundation Trust)
Written by: Rebecca Downing and Dr. Caroline Williams-Gray