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Gout drug might reduce risks of 3 prevalent neurodegenerative diseases

People with the inflammatory arthritis gout are unlikely to call it a blessing.

But research in the journal PLOS ONE suggests allopurinol, a medication used to prevent gout flares, could lower people’s risks of developing Alzheimer’s, Parkinson’s and Lou Gehrig's disease.

The findings link the gout drug allopurinol to 13%-34% lower risk for each neurodegenerative disease (ND), and a 23% overall reduction in risk of the three diseases.

“We have exciting new potential treatment options to slow progression of the three most common neurodegenerative diseases using inexpensive medications that are already FDA approved and could be repurposed if follow-up clinical trials support our findings,” said co-author Dr. Brad Racette, chair of neurology at Barrow Neurological Institute.

The study looked at data from more than 330,000 Medicare beneficiaries aged 66-90. As the only national health care systems in the U.S., Medicare and Medicaid are often viewed as representative of the population at large.

When scientists compared treatment targets in the body and how drugs affected them, they found both allopurinol and the beta blocker carvedilol, which also reduces ND risk, block an enzyme called xanthine dehydrogenase.

Racette said if they’d thought in terms of drug categories rather than combining medications by their primary and secondary mechanisms of action, the team likely would have missed carvedilol’s effects on ND risks.

“And the reason we say that is because we followed people forward in our control population for five years who were taking carvedilol or other related beta blockers that did not have that same effect,” he said. “It suggests that there's something unique about carvedilol, and what we think is it has an off-target effect on the xanthine dehydrogenase enzyme.”

Previous research links that enzyme to oxidative stress, a condition some believe is common among the three diseases.

“Oxidative stress in the brain is different than the stress that we experience when we have major life events,” said Racette. “It’s more related to metabolic stress in the body.”

Racette worked on the study with former colleagues at Washington University in St. Louis and University of the Witwatersrand in Johannesburg, South Africa.

After finding the “target-action pairs,” the team further tested the drugs’ effects by following a cohort of subjects over five years.

“We looked medications that people were taking two years prior to their diagnosis so that we were not focusing on medications that might have been used only as people got very close to their diagnosis year,” said Racette.

The chemotherapy drug methotrexate also showed promise, but its signal was weaker, and its effects relied on a different mechanism than allopurinol and carvedilol. Nailing down its effects and mechanisms will require more research.

“I think methotrexate still remains a drug of interest, but the replication results weren't as robust as for allopurinol and carvedilol,” said Racette. “Both were quite robust, even in our replication studies.”

Racette said the findings suggest exciting questions for future research.

“If you are diagnosed with one of these diseases, do the medications slow the progression of the disease? That's the bridge we need to cross next,” he said.

Nicholas Gerbis joined KJZZ’s Arizona Science Desk in 2016. A longtime science, health and technology journalist and editor, his extensive background in related nonprofit and science communications inform his reporting on Earth and space sciences, neuroscience and behavioral health, and bioscience/biotechnology.Apart from travel and three years in Delaware spent earning his master’s degree in physical geography (climatology), Gerbis has spent most of his life in Arizona. He also holds a master’s degree in journalism and mass communication from Arizona State University’s Cronkite School and a bachelor’s degree in geography (climatology/meteorology), also from ASU.Gerbis briefly “retired in reverse” and moved from Arizona to Wisconsin, where he taught science history and science-fiction film courses at University of Wisconsin-Eau Claire. He is glad to be back in the Valley and enjoys contributing to KJZZ’s Untold Arizona series.During the COVID-19 pandemic, Gerbis focused almost solely on coronavirus-related stories and analysis. In addition to reporting on the course of the disease and related research, he delved into deeper questions, such as the impact of shutdowns on science and medicine, the roots of vaccine reluctance and the policies that exacerbated the virus’s impact, particularly on vulnerable populations.