Parkinson’s disease is a common neurological disease leading to increasing disability but currently we do not have any treatments to slow down its progression. Research suggests that the immune system is involved in this progression, and we have just completed a clinical trial (AZA-PD) of a drug called azathioprine, which dampens down the immune system.

We did not see a beneficial effect from treatment with azathioprine on our prespecified “primary outcome”, which was a score assessing posture, balance and walking. However, in additional “exploratory” analysis, participants who took azathioprine showed an improvement in symptoms related to difficulty with movement. When we separate out female participants, we see evidence of a more widespread positive effect, and findings which suggest that their immune systems responded differently to the medication. There is a good rationale for why there might be these sex-related differences. It is well established that there are differences in the immune system between men and women, and this is just starting to be explored in Parkinson’s disease.

My project will explore the difference in the response to azathioprine between male and female participants using samples and data collected during the trial. This includes a detailed panel of 250 immune markers in the blood and cerebrospinal fluid, and imaging which assessed the activation of immune cells in the brains of participants. The next stage of the project will involve recruiting new patients to donate blood samples, and look at the response of their immune cells to azathioprine in the laboratory, to see if there are differences between men and women.

The overall aim of this project is to understand the reason behind the different treatment response in men and women in AZA-PD, because this will help us to design the next study targeting the immune system in Parkinson’s disease.

Figure 1: Selected figures from the AZA-PD trial showing change in clinical scores (MDS-UPDRSI and II-A&B) and immune cell numbers (C&D) in azathioprine and placebo groups, stratified by sex