Stratifying deeply phenotyped Parkinson’s patients with blood-based immune signatures

Drs Cynthia Sandor, who is supported by the Ser Cymru II programme which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government, Kathryn Peall and Professor Caleb Webber have recently received funding from the Health and Care Research Wales Health PhD Studentship awards to investigate the role of inflammation in Parkinson’s disease, as part of the Dementia Research Institute and BRAIN unit at Cardiff University.

Parkinson’s disease is the most common neurodegenerative movement disorder, estimated to affect ~8000 people in Wales. However, considerable phenotypic heterogeneity, both in presentation and symptom progression, is observed in clinical practice. In order to better understand these differences Dr Sandor has developed a computational model that allows integration of genetic and clinical information, from which she has identified symptom sub-groups that mirror those that are seen in clinical practice. As part of this work, those patients with a greater genetic risk towards Alzheimer’s disease tended towards developing a more severe form of Parkinson’s disease, as well as demonstrating a more rapid progression of their symptoms over time.

Alzheimer’s disease research has highlighted the potential contribution of multiple components of the neuroinflammatory system in disease mechanism. To date, the role of these immune components has not been investigated in Parkinson’s disease, in particular how they might contribute to the differing symptoms and disease severity levels of disease severity. This project plans to make use of already collected, highly detailed, clinical and genetic information involving the Michael J Fox funded Parkinson’s Progression Markers Initiative (PPMI) and Accelerating Medicines Partnership (AMP)-PD. UK based cohorts – the UK Tracking cohort and UK Discovery cohort – will also be used in the development of machine learning approaches that may enable earlier identification of patients with more severe forms of Parkinson’s disease, with this having the potential to better plan clinical care.

Dr Cynthia Sandor said "Our aim is to accelerate our understanding of how Parkinson's disease varies across individual patients and to identify blood-based biomarkers that will aid the disease course prediction, aid care planning. An understanding of the immune system, how the body is reacting to the disease, is clearly important for Parkinson's disease. This research offers molecular insights that could guide the development of therapeutics able to alter the progression and manifestation of an individual’s Parkinson’s disease. Disease modifying therapies are more readily clinically trialled than preventative therapies for neurodegenerative diseases and thus are more likely to have a quicker impact on patients and their families."

This forms an exciting PhD opportunity, using cutting edge computational approaches. It also represents a new working partnership between bioinformatics (Dr Sandor and Prof Webber) and clinical (Dr Peall) teams, aiming to ensure directly relevant application of novel genetic data to clinical practice.