Allantoin may hold promise as prognostic biomarker in Parkinson’s

First study of molecule finds high levels in patients' blood

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A molecule associated with oxidative stress, called allantoin, is found at higher levels in the blood of people with Parkinson’s disease relative to their peers without the neurodegenerative disorder, according to a new study.

Allantoin and its ratio to uric acid (UA) — the antioxidant molecule from which it’s derived — also were linked to non-motor symptoms of Parkinson’s, including REM sleep behavior disorder (RBD).

Oxidative stress is a type of cellular damage that’s been implicated in Parkinson’s disease progression. As noted by the researchers, these findings suggest that, by reflecting the degree of an individual’s oxidative stress, allantoin may hold promise as a prognostic biomarker in Parkinson’s.

“To our knowledge, this is the first study investigating allantoin and allantoin/UA ratio in … [Parkinson’s disease] patients,” the team wrote.

The study, “Serum but not cerebrospinal fluid levels of allantoin are increased in de novo Parkinson’s disease,” was published in npj Parkinson’s disease.

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Oxidative stress occurs when there is an imbalance between toxic reactive oxygen species and the antioxidant molecules needed to combat them. It has become increasingly recognized that this may be one of the key processes underlying the death of dopamine-producing nerve cells in Parkinson’s.

Uric acid is a potent, naturally produced antioxidant. It’s been found at lower levels in people with Parkinson’s disease relative to healthy people, and higher levels are linked to protection against cell loss and Parkinson’s symptoms.

Under oxidative stress conditions, uric acid is converted into a molecule called allantoin. It’s thus thought that allantoin may be a good biomarker of oxidative stress, but few studies have evaluated its potential role in Parkinson’s.

The researchers previously found that allantoin and the allantoin-to-uric acid ratio were elevated in people with REM sleep behavior disorder, called RBD. This sleep disorder commonly appears in the years before a Parkinson’s diagnosis, known as the prodromal phase.

However, a study by other scientists did not find any difference in allantoin levels between Parkinson’s patients and their healthy peers.

Now, this team sought to further investigate the potential roles of allantoin and/or uric acid as oxidative stress biomarkers among 86 Parkinson’s patients included in a long-term project dubbed BIO-PD. In this project, the team is collecting samples from Parkinson’s patients who were not yet treated with dopamine-replacing therapies.

The group comprised 33 women and 53 men, who had a mean age of 57.9. Also included in the analysis were 40 people without Parkinson’s, who served as a control group.

Samples of blood and cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — were analyzed for allantoin, uric acid, and the ratio between the two.

Allantoin levels and the allantoin/uric acid ratio were found to be significantly elevated in the blood of patients relative to samples from the controls, perhaps reflecting “increased oxidative stress” in Parkinson’s, according to the researchers.

They noted that the 45% increase in allantoin observed in the Parkinson’s group was smaller in comparison to that seen in their prior study of people with RBD, who demonstrated an 86% increase in blood allantoin levels. Given that RBD is often reflective of a prodromal, or very early stage of Parkinson’s, that discrepancy could mean that high allantoin is “most pronounced in the prodromal phase and gradually declines during later disease stages,” the researchers wrote.

In contrast, allantoin was not elevated in the CSF of the 51 Parkinson’s patients with available samples compared with the control group. However, allantoin levels may rise later in the CSF as the disease progresses, the team noted.

Uric acid levels were not associated with Parkinson’s disease in the blood or CSF, in contrast to prior studies that found lower uric acid levels in the neurodegenerative disease.

We can speculate that higher oxidative stress levels herald a more severe course in the early stage of disease and it may be worth to further study allantoin/UA ratio as a prognostic biomarker in [Parkinson’s].

Among Parkinson’s patients, a higher allantoin/uric acid ratio in the blood or CSF was associated with higher scores on the Scales for Outcomes in Parkinson’s Disease – Autonomic Dysfunction (SCOPA-AUT), a measure of autonomic symptoms, or those related to dysfunction of the nerves involved in involuntary bodily functions.

The relationship between autonomic dysfunction and a higher allantoin/uric acid ratio was largely driven by urinary or gastrointestinal symptoms, according to the researchers.

Allantoin and allantoin/uric acid ratios in the CSF also were higher among people who had been living with Parkinson’s for a longer time. Moreover, the 21 Parkinson’s patients with RBD had significantly higher ratios in both fluids relative to people without the sleep disorder.

The researchers noted that findings linking these molecules to Parkinson’s symptoms are “exploratory and need to be treated with caution.”

Still, “we can speculate that higher oxidative stress levels herald a more severe course in the early stage of disease and it may be worth to further study allantoin/UA ratio as a prognostic biomarker in [Parkinson’s],” the researchers wrote.