Allopurinol significantly lowers risk for neurodegenerative diseases

The findings of the study are published in PLOS ONE

With ageing and increasing life expectancy, the prevalence of neurodegenerative diseases like Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) are increasing.

There is an urgent need to identify disease-modifying therapies. Therapeutic modalities primarily focus on symptom management. Pharmaceutical treatments can emerge through new drug synthesis or the repurposing of existing drugs. The latter is cost-effective due to the well-established pharmacokinetic and safety profiles of FDA-approved medications.

Adding data further, researchers in this study screened medications based on biological targets and pharmacological actions on those targets rather than as individual drugs.

They hypothesized that the three neurodegenerative diseases share some common mechanisms and that evidence of medications tied to lower risk would represent high-priority candidates for disease-modifying clinical trials.

The team identified prescription medications for lower risk of three neurodegenerative diseases in this study: PD, AD and ALS.

The key findings of the study are:

• Researched used medication data from 2006–2007 and categorized all filled medications based on biological targets and mechanisms of action on those targets.
• They used multinomial logistic regression models and attempted replication in a cohort study, including an active comparator group.
• They found the most consistent inverse association across both studies and all three neurodegenerative diseases for xanthine dehydrogenase/oxidase blockers.
• The gout medication, Allopurinol, represented this.
• Allopurinol lowered risk by 13–34% for each neurodegenerative disease group.
• There was a 23% reduction in neurodegenerative disease in the fifth year of follow-up when comparing allopurinol users to non-users.
• There were parallel associations for a related target-action pair unique to carvedilol.

The Key strengths of the study were restriction to incident cases and application of exposure lagging through our exclusion of medications used in the years immediately before diagnosis with a neurodegenerative disease.

Finally concluding, researchers said that we identified a target-action pair association with a lower risk of developing neurogenerative diseases like PD, AD, and ALS while classifying medications based on specific action on their biological targets.

They wrote that blockade of xanthine dehydrogenase/oxidase or its effects modestly reduced the risk of all three neurodegenerative diseases.

Further reading:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285011