Disruptions in Purine Metabolism Cited in Parkinson’s Development

Parkinson’s disease is a neurodegenerative condition that affects an individual’s brain, causing issues with their movement, sleep and mental health. Common symptoms include tremors, slowed movements and issues with balance.

For years, researchers have observed reduced uric acid levels in Parkinson’s disease patients. Uric acid is created when the human body breaks down purines, which are produced in the body. In the past, scientists posited that uric acid, which possesses antioxidant properties, played a role in decreasing oxidative stress in the brain.

Now, new research has unveiled new insights into how patients with Parkinson’s disease suffer metabolic disruptions. Scientists began by obtaining samples of cerebrospinal fluid and blood from patients with Parkinson’s. They then conducted an analysis of the samples, using targeted metabolomics to evaluate levels of purine metabolites such as xanthine, hypoxanthine, inosine and uric acid. The researchers found serious impairments in adenosine triphosphate (ATP) recycling and purine metabolism.

ATP is responsible for producing energy in cells. The recycling and breakdown of this triphosphate is key for maintaining healthy function of cells. In Parkinson’s patients, this seems to be malfunctioning, causing an energy deficit that may aggravate the condition’s symptoms.

The scientists also discovered that Parkinson’s patients had considerably lower uric acid levels in both cerebrospinal fluid and serum in comparison to the control group. Additionally, hypoxanthine levels were also low. The study’s lead author, Dr. Hirohisa Watanabe, stated that this meant that the link between Parkinson’s and uric acid was more complex than prior studies had found.

Watanabe explained that uric acid levels in cerebrospinal fluid and serum weren’t directly associated with higher concentrations of xanthine, which suggests that there’s more that influences the disease beyond conventional purine metabolism pathways. He added that the observed decrease in cerebrospinal fluid inosine could also reflect a drop in the production of nucleotides in the central nervous system. This, he noted, could have severe implications for the production of energy in the brain.

In their report, the scientists linked the decreased levels to sex, age and body weight instead of xanthine, challenging previous assumptions about purine metabolism. This study brings the research field one step closer to better understanding the metabolic changes involved in Parkinson’s. This may enable the development of new treatments that improve the quality of life of patients while also slowing disease progression. The scientists are now focused on looking into nutritional interventions and exercise as potential ways to improve ATP recycling and energy metabolism.

The research’s findings were published in “NPJ Parkinson’s Disease.”

The R&D programs of enterprises that are focused on developing better therapeutics targeting Parkinson’s disease, such as Clene Inc. (NASDAQ: CLNN),  will hopefully benefit from the growing body of scientific literature documenting the different factors that contribute to the onset and progression of this disease.

NOTE TO INVESTORS: The latest news and updates relating to Clene Inc. (NASDAQ: CLNN) are available in the company’s newsroom at https://ibn.fm/CLNN

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