Results from AZA-PD, a proof-of-concept trial investigating immunosuppression as a new treatment approach for Parkinson’s disease, have been published in Lancet Neurology by a team from Cambridge University.
Twenty years ago, no one would have considered using an immune-acting drug in Parkinson’s disease. But work across the world, including in Cambridge, has shown how important the immune system is in the progression of Parkinson’s.
The trial used a drug called azathioprine, an immunosuppressant which is currently used to treat other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease. Although the study did not find a beneficial effect of azathioprine on the main outcome measure of walking and balance, it did show that participants who were treated with azathioprine had an improvement in symptoms related to movement, including tremor, speech and day-to-day tasks such as getting up, washing and dressing. It also showed that female participants had more widespread benefits from treatment.
Whilst this is not sufficient evidence to support the use of azathioprine as a treatment for Parkinson’s, it is very promising, and supports this avenue of research and the need for further trials targeting the immune system in Parkinson’s disease.
The researchers advise that patients should not try to acquire azathioprine as it is not recommended as a treatment yet. The study was an early proof-of concept trial, with mixed results. More research is needed in larger studies to understand the effects of immunosuppressant treatments in Parkinson’s.
Read the results of AZA-PD in Lancet Neurology
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
The full results of AZA-PD, a randomised double-blind placebo-controlled clinical trial of azathioprine in early Parkinson’s disease, are now available online through Lancet Neurology.
This trial was led at Cambridge University’s Department of Clinical Neurosciences by Dr Caroline Williams-Gray with co-investigator Dr Julia Greenland. It is the first to show a potential beneficial effect of a broadly-acting immunosuppressant drug in Parkinson’s disease.
The AZA-PD study participants were treated with azathioprine or a placebo for one year to investigate whether azathioprine could have a beneficial effect on the clinical progression of Parkinson’s disease.
The study authors looked at a range of symptoms which are linked to Parkinson’s disease, but they had specifically hoped to see whether the treatment could improve a score which assesses posture, balance and walking. This was the “primary outcome” of the trial. Although azathioprine didn’t have a beneficial effect on this score, the results did show positive effects on other aspects of the disease.
When participants were asked about symptoms relating to movement problems – such as difficulty with speech or tremor, and how easy it is to get out of a chair, use cutlery, wash and dress – they showed that the participants taking azathioprine scored significantly better. The improvements were greater in women than men, and women also showed more improvement on non-motor symptoms of Parkinson’s such as fatigue, mood changes and sleep problems, as well as on overall quality of life. Another significant finding was that patients with faster-progressing Parkinson’s disease showed signs of improved memory and thinking skills.
Azathioprine is a drug which predominantly acts on the peripheral immune system, and does not cross from the bloodstream into the brain. One of the goals of the study was to look at whether suppressing the peripheral immune system would have an impact on inflammation in the brain in Parkinson’s. The authors assessed this by measuring immune cells in lumbar puncture samples, as well as the blood, before and after treatment, and a proportion of participants also had PET brain scans to measure inflammation in the brain. The results showed that azathioprine treatment reduced immune cells in the blood and the spinal fluid, and also reduced the spread of brain inflammation. This is an important finding which supports the approach of testing drugs which act on the peripheral immune system for Parkinson’s.
Overall, the study does not give enough evidence to recommend immunosuppressive drugs for Parkinson’s disease yet, but it does indicate that targeting immune activation might be a useful strategy for the treatment of Parkinson’s. There are currently no therapies which cure or slow down the progression of Parkinson’s disease, so this an exciting avenue, which needs more research to confirm the best approach.
Dr Julia Greenland commented:
“We are really excited to share these promising results from our trial. We hope that this will prove to be just one of the first steps in targeting the immune system in Parkinson’s, and this pathway will lead to new treatments for the disease. We are incredibly grateful to all of our participants who put their trust in us and took part in AZA-PD, and without whom we would be no closer to understanding Parkinson’s.”
Dr Caroline Williams-Gray commented:
“The AZA-PD trial follows many years of research suggesting that immune activation is an important contributor to Parkinson’s disease. We are really encouraged by the results which suggest that immunosuppression impacts on both brain inflammation and symptoms – and importantly the trial has shown that testing immunosuppressive drugs in Parkinson’s is feasible and safe. Overall, our findings provide strong support for further trials targeting the immune system in Parkinson’s.”
Adapted from: Clinical Neurosciences News
Posted on 07/01/2026
