Immunosuppressive therapy and Parkinson's disease risk

Date of Approval: 
2016-06-22 00:00:00
Lay Summary: 
Parkinson's disease (PD) is a common neurological disorder affecting movement, walking and memory. It is caused by loss of brain cells which produce a neurotransmitter called dopamine. The reason these cells are damaged is not fully understood. One factor that may be involved is an overactive immune response. We aim to investigate whether drugs which suppress the immune system reduce risk of developing PD. To do this, we will look at historical information stored in CPRD about individuals who have ever taken strong immunosuppressant drugs for other conditions (e.g. Rheumatoid arthritis, inflammatory bowel disease) and determine how many of these individuals go on to develop PD. These individuals are likely to differ from the general population in terms of characteristics such as age and general health, which may complicate any apparent relationship between immunosuppressant drug use and PD risk. We will therefore describe these characteristics in detail, and use this information to design a second phase of the study to compare PD risk in those exposed to immunosuppressant drugs versus those who have never taken these drugs but are otherwise well-matched. This work is important because it may pave the way for immunosuppressant therapies to slow the development of PD.
Technical Summary: 
Parkinson's disease (PD) is a neurodegenerative disorder which affects movement and walking as well as cognition, leading to considerable disability. The underlying pathology involves deposition of alpha-synuclein aggregates within the brain and neuronal loss, particularly within dopaminergic networks. However, immune activation is also well described in PD, both in the brain and the periphery, and may contribute to disease initiation and progression. Hence we will investigate whether immunomodulatory drugs alter PD risk, a question which has important implications for the use of such drugs as novel disease-modifying agents to slow disease progression. However there are challenges in addressing this question using epidemiological data, as both exposure to these drugs and the outcome of PD are relatively rare, and those on immunosuppressive therapy will have significant comorbidity which may be a confounding factor. The first phase of this work will therefore involve a descriptive study of the demographic and clinical characteristics of all cases within the CPRD database exposed to immunosuppressive drugs, as well as PD incidence in this cohort. We will use the data to determine the feasibility of a comparative cohort study and subsequently identify an appropriate control cohort and relevant confounding factors for this comparative study.
Health Outcomes to be Measured: 
Incident diagnosis of Parkinson's disease occurring at least 6 months (180 days) after the first prescription of immunosuppressive therapy.
Application Number: 

Caroline Williams-Gray - Chief Investigator - University of Cambridge
Carol Brayne - Collaborator - University of Cambridge
Catherine Saunders - Collaborator - University of Cambridge
Kirsten Scott - Collaborator - University of Cambridge
Rupert Payne - Collaborator - University of Bristol