Immune suppression proposed as way to slow Parkinson’s progression
Researchers tested azathioprine to see if it reduced brain inflammation
Suppressing the immune system to reduce brain inflammation, a known contributor to Parkinson’s disease progression, may offer a promising new strategy for slowing the disease, early trial results suggest.
Specifically, azathioprine, a commonly used drug that suppresses immune activity, reduced motor symptoms and improved cognitive function in people with early-stage disease.
Preliminary results from the Phase 2 AZA/PD trial (ISRCTN14616801) were presented in an oral session titled, “Azathioprine for Parkinson’s disease: A randomised double-blind placebo-controlled trial (AZA-PD),” at this year’s  International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and Related Neurological Disorders.
“There are currently no therapies available to cure or slow the progression of Parkinson’s disease. We know that inflammation in the brain is a factor, but this is the first time we’ve been able to show that we can address this by suppressing the immune system with the potential to deliver benefits for patients,” Caroline Williams-Gray, PhD, study leader and principal research associate at the Department of Clinical Neurosciences at the University of Cambridge, said in a news story.
Parkinson’s is a progressive neurodegenerative disorder caused by the gradual loss of nerve cells that produce dopamine, a brain chemical involved in motor control. As dopamine levels fall, patients have various motor symptoms, such as tremors, rigidity, and slowness of movement, or bradykinesia.
Existing treatments focus on managing symptoms rather than slowing or halting disease progression. While dopaminergic therapies like levodopa alleviate motor symptoms by replenishing dopamine, they don’t adequately address nonmotor symptoms, such as problems with balance, mood changes, or cognitive decline, which stem from broader damage in the brain.
Emerging research suggests the immune system may play a significant role in Parkinson’s progression and chronic neuroinflammation is increasingly recognized as contributing to ongoing neuronal damage. This makes the immune system an attractive target for potential disease-modifying therapies.
Slowing Parkinson’s progression with immune system suppression
University of Cambridge researchers are testing if azathioprine can help slow Parkinson’s progression by suppressing the immune system. The study is funded by the Cambridge Centre for Parkinson-Plus and Cure Parkinson’s. Azathioprine, which is sold as Azasan, Imuran, and generics, and often used in immune-related conditions like multiple sclerosis and rheumatoid arthritis, is a purine-like compound that interferes with the production of nucleic acids, the building blocks of DNA, needed for immune cell proliferation.
AZA/PD enrolled 66 people with early-stage Parkinson’s who were considered at a high risk of disease progression, but didn’t have other inflammatory or immune conditions. The participants were randomized to receive either azathioprine or a placebo daily for a year, followed by a six-month monitoring period. Azathioprine was administered as a tablet, starting at 1 mg/kg and increased to 2 mg/kg after a month if blood tests and clinical assessments allowed it.
The study participants had regular monitoring visits every two weeks initially, with adjustments to the dose based on clinical profiles such as blood results and adverse events. Monitoring intervals were extended to every three months once the participants were stable.
The primary goal was to assess changes in walking ability and core movement functions, such as balance and posture, over a year using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) in the period when the medications are least effective and symptoms more apparent, called the off state. A score was calculated using the sum of specific items within Part III of the MDS-UPDRS, including assessing speech, facial expression, rising from a chair, walking ability, postural stability, and bradykinesia.
Additional outcomes included assessing motor and cognitive functions, nonmotor symptoms such as mood changes or sleep disturbances, and quality of life, as measured through questionnaires and clinical evaluations. The study also collected blood and cerebrospinal fluid samples to monitor immune marker changes, along with PET scans to detect brain inflammation.
Those who received azathioprine reported fewer motor symptoms and improvements in walking, dressing, washing, and writing. These gains seemed to be greater in women. Also, the patients with more aggressive forms of Parkinson’s showed enhanced cognitive function, including better memory and thinking.
While azathioprine couldn’t cross the blood–brain barrier, which is the semipermeable membrane that protects the brain from infections and blocks many medications, it acted indirectly to slow brain inflammation. The results showed it suppressed immune activity, this way helping to reduce inflammatory signals reaching the brain.
There were no major safety concerns related to immunosuppressive therapy.
Williams-Gray is also leading a study called DAPA-PD that will soon start recruiting participants to test whether dapansutrile, an anti-inflammatory compound, might be safe and efficient in Parkinson’s.
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