AZA-PD was a phase 2 clinical trial of azathioprine – an immunosuppressant medication – to evaluate its safety and ability to lower neuroinflammation in people with Parkinson’s.
About the study
Dr Caroline Williams-Gray at the University of Cambridge led a phase 2 clinical trial of azathioprine (AZA-PD) – an immunosuppressive drug currently used to treat autoimmune conditions, such as rheumatoid arthritis. This trial involved 66 people with early-stage Parkinson’s (diagnosed <3 years before recruitment) taking azathioprine or a placebo (dummy drug) for 12 months. The researchers aimed to evaluate if azathioprine can “correct” the Parkinson’s immune profile and slow progression of the condition by suppressing immune activity in the brain and body. They also compared the immune profiles of participants with age-matched controls to get a better idea of how this differs in people with Parkinson’s.
Cure Parkinson’s funded a sub-study of this trial, which aimed to better understand azathioprine’s mechanism of action (MoA), or what a drug interacts with in the body to achieve the desired effect. To do so, the researchers used brain imaging, alongside analyses of blood and cerebrospinal fluid (CSF; the fluids surrounding the brain and spinal cord) samples to determine whether azathioprine lowered immune activity. Samples were collected at the initial, 12-month, and 18-month follow-up visits.
This study concluded in early 2025 and the results are now published.
Trial overview
- Researcher: Dr Caroline Williams-Gray
- Institution: University of Cambridge
- Project Type: Clinical Trial, Phase 2
- Status: Completed
- Dates: February 2020 – February 2025 (delayed due to COVID-19)
- iLCT-evaluated (2017)
- Therapy Target: Neuroinflammation
More about the study
What is azathioprine?
Azathioprine is an immunosuppressant, meaning it lowers activity of the immune system. There is growing evidence to support that neuroinflammation, or inflammation in the brain, may be a driver of Parkinson’s progression. Inflammation is one of the body’s natural immune responses; however, chronic, or long-term, inflammation can lead to damage of normal cells.
Studies have suggested that the immune system may be over-active in people with Parkinson’s, meaning neuroinflammation could be contributing to the loss of dopamine nerve cells (neurons) experienced in Parkinson’s. Therefore, researchers are now interested in therapies, like azathioprine, which may be able to lower neuroinflammation, and their potential to slow Parkinson’s progression.
What are the results?
Although some participants did report improvements, the researchers did not find a clinically significant difference between the motor symptoms of people taking azathioprine and those taking the placebo. This means that the trial, unfortunately, did not meet its primary endpoint. Additionally, any positive effects seen during the trial did not persist after stopping the treatment, indicating that azathioprine did not have a lasting effect on Parkinson’s progression.
The team did, however, identify several sub-populations who may have responded better to azathioprine. For example, they saw greater beneficial effects in women. This finding is of particular interest as women are often under-represented in Parkinson’s research, and autoimmune conditions are also more common in women. Researchers also found that participants with faster-progressing Parkinson’s showed signs of improved memory and thinking. Although these outcomes are interesting, this was a small, proof-of-concept trial, meaning they will need to be validated in larger, more robust clinical trials.
Video presentation – Dr Caroline Williams-Gray discusses the trial
Further information
Publications
- Azathioprine for the treatment of early Parkinson’s disease (AZA-PD) – https://doi.org/10.1016/S1474-4422(25)00386-2
Results from the phase 2 AZA-PD trial are now published
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