Objective: To design a clinical trial to test the concept that the immune system is integral in the progression of Parkinson’s disease (PD) and establish peripheral immune activation as a target for disease modifying therapies

Background: Variations in immune-related genes are related to PD risk and the use of immunosuppressant medication reduces this risk. Neuroinflammation occurs in the brain in PD with activation of microglia, the brain’s innate immune cells, and infiltration of lymphocytes from peripheral blood into the brain parenchyma. Immune cells in the blood show an activated profile, and lymphocytes specifically respond to alpha synuclein. Patients with early-stage PD have a pro-inflammatory immune profile in the blood, and this is linked to faster disease progression. We hypothesize that suppression of peripheral immune activation will reduce brain inflammation and PD progression.

Method: AZA-PD is a phase II randomised placebo-controlled double-blind trial of azathioprine for PD. Azathioprine is a peripherally-acting immunosuppressant drug commonly used for inflammatory disorders, with a well characterised safety monitoring protocol. Sixty participants, within three years of diagnosis and with no inflammatory or immune comorbidity, will be randomised to receive azathioprine or placebo (1:1) for 12 months, with a further 6-months follow-up. Clinical outcomes will be evaluated six-monthly, with more frequent safety monitoring. The primary outcome is the change in the MDS-UPDRS gait/axial score in the OFF state over 12 months. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. Peripheral and central immune activation will be investigated through immune marker analysis, immunophenotyping of mononuclear cells in blood and CSF and PK-11195 PET imaging both pre and post treatment.

Results: The study was approved by the London-Westminster REC (ref 19/LO/1705) and accepted by the MHRA for a clinical trials authorisation (ref CTA 12854/0248/001-0001). Details are also available on the following registries: ISRCTN14616801, EudraCT-2018-003089-14.

Conclusion: The trial opened in March 2020 but recruitment was suspended due to the COVID-19 pandemic. Following protocol amendments to mitigate COVID-19 risk, recruitment is scheduled to begin in April 2021.

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/azathioprine-immunosuppression-and-disease-modification-in-parkinsons-disease-aza-pd-a-randomised-double-blind-placebo-controlled-phase-ii-clinical-trial/