UK trial has found that azathioprine does not slow progression in early Parkinson’s disease, despite good tolerability. The results highlight both the challenges and promise of immune-based strategies for modifying disease course.
Immune Targets in Early Parkinson’s Disease
Growing evidence suggests that immune dysfunction plays a role in the development and progression of early Parkinson’s disease. While current treatments effectively manage symptoms, none are proven to alter long term neurodegeneration. This has led researchers to explore whether broadly acting immunosuppressive therapies might influence disease trajectories by dampening harmful immune responses in vulnerable neural pathways.
Phase 2 Trial in Early Parkinson’s Disease
The AZA-PD study was a randomised, double blind, placebo controlled, proof of concept phase 2 trial conducted at a single specialist clinic in Cambridge, UK. Participants aged 50 to 80 years were within three years of Parkinson’s diagnosis and were randomly assigned to receive daily oral azathioprine at 2 mg per kg or placebo for 12 months. Between May 2021 and July 2022, 78 individuals were screened and 66 were randomised, with 32 receiving azathioprine and 34 placebo. The intention to treat population included 23 women and 43 men. At 12 months, the mean change in the MDS UPDRS gait axial score was 0.54 points with azathioprine and 0.13 points with placebo, yielding an effect size of 0.438 with a 95% confidence interval from -0.694 to 1.57 and a p value of 0.78. A total of 159 adverse events occurred in the azathioprine group and 156 in the placebo group. Serious adverse events were reported in eight participants receiving azathioprine and four receiving placebo. Infections and gastrointestinal disorders were the most common events in both groups.
Implications for Clinical Practice
Although azathioprine did not meet the primary endpoint, the findings confirm feasibility and safety of immune focused trials in early Parkinson’s disease. Exploratory signals in immune biomarkers and possible sex specific effects suggest that more targeted or personalised immune interventions may still hold potential. Future studies may refine patient selection and immune targets to better address disease modification.
Reference
Greenland JC et al. Azathioprine for the treatment of early Parkinson’s disease (AZA-PD): a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. The Lancet Neurology. 2026;25(1):39-49.
