Research

First demonstration that immunosuppression may help to slow Parkinson’s progression

April 16 2025

In our January newsletter we signposted some key milestones coming up during 2025, including some eagerly anticipated clinical trial results. One of these was the AZA-PD trial, conducted in Cambridge, UK, led by Dr Caroline Williams-Gray, and funded by our good friends at Cure Parkinson’s. The trial investigated whether the drug azathioprine, which suppresses the immune system, could potentially slow the progression of Parkinson’s disease. The trial concluded last year, and the results were recently presented at the International Conference on Alzheimer’s and Parkinson’s Disease and Related Neurological Disorders (affectionately known as AD/PD), which was held earlier this month in Vienna, Austria (April 1–5, 2025). The results were presented by Dr Julia Greenland, a neurology specialist trainee at Cambridge University Hospitals NHS Foundation Trust and clinical research fellow at the University of Cambridge (pictured below with Dr Williams-Gray; Dr Greenland is on the right).

The results of the trial revealed, for the first time, that immunosuppression could have a beneficial effect on Parkinson’s disease, with overall improvements in movement-related symptoms observed in those who took azathioprine. This is hugely exciting, and these results pave the way to a larger phase III study (the AZA-PD study was a phase II ‘proof of concept’ study that enrolled 66 people with early-stage Parkinson’s, half of whom received the treatment with the other half receiving placebo). But before diving into the results, it is worth touching on why immunosuppression might be beneficial for Parkinson’s.

Some degree of inflammation is a natural response to injury or infection—our immune system uses the inflammatory response to protect us from attack, to remove all kinds of nasties, and to drive healing. This is all normal and essential to keep us healthy. However, too much inflammation (or sustained inflammation over a long period of time) can be unpleasant or harmful. We all experience this when we experience the symptoms of a common cold or swelling around a sprained joint; more extreme conditions caused by an out-of-control immune system include severe allergies and auto-immune conditions that can be fatal. Inflammation (both localized neuroinflammation in the brain and peripheral inflammation driven by activation of the immune system) has been linked to neurodegenerative disorders including Alzheimer’s and Parkinson’s disease. Hence, strategies targeting the immune system to reduce inflammation are attractive as a potential means of reducing the damage that occurs in these disorders. Based on increasing evidence that the immune system plays an important role in driving the loss of neurons in Parkinson’s, the AZA-PD investigators proposed that targeting the immune system might be an effective way to slow Parkinson’s disease progression.

Azathioprine is used as an immunosuppressant drug in clinical practice to treat auto-immune conditions as diverse as rheumatoid arthritis, Crohn’s disease, lupus and multiple sclerosis. There are a number of immediate advantages to using azathioprine to assess the effect of immunosuppression on Parkinson’s progression: it is relatively cheap; it is easy and practical for patients to take (once-daily oral administration); it has been shown to be safe and well-tolerated; and it has shown good efficacy in a range of other conditions. While azathioprine cannot get into the brain (it can’t cross the blood–brain barrier, like many drugs), it dampens the effects of the immune system, which in turn reduce inflammation in the brain.

The AZA-PD trial investigators investigated the effect of azathioprine on the disease course over 12 months of treatment, and whether any effects were maintained over a 6-month follow-up period. They also examined the impact of azathioprine on various parameters of immune activation, and the relationship between these parameters and clinical measures of disease progression. The trial participants were all aged between 50 and 80 years, with a disease duration of <3 years (early-stage Parkinson’s). Participants were allowed to continue taking their Parkinson’s medications, as prescribed, and dose adjustments were permitted.

The participants who received azathioprine showed improved movement-related symptoms, noting that they found it easier to perform tasks such as moving around, writing, washing, and dressing. Notably, the observed improvements were greater in female participants than in males. Among those with faster-progressing disease, those receiving azathioprine also showed better performance on memory and cognitive tests. Based on these promising results and no significant safety concerns being raised, the path is now clear to move into larger-scale studies of efficacy. We look forward to the study publication and to hearing more about plans for future studies.

While the incremental progress of research and multiple steps to approval that are required may feel slow and frustrating to patients who want disease-modifying therapies now, the step-by-step building of evidence is necessary to keep patients safe. New drugs need to be thoroughly tested to ensure that they are not only safe, but also better than the alternatives. This study represents a big step forward for those studying the potential of using immunosuppression to treat neurodegenerative conditions, which is just one of many strategies currently under investigation. With each step forward, we come closer to a cure.