Wednesday October 14 2009
People with Parkinson's disease often have difficulty walking
Researchers have concluded that urate, a naturally occurring chemical in the blood that is known to cause gout, “appears to slow the progression of Parkinson's disease”, BBC News has reported. Researchers claim that urate is a potent antioxidant and “counteracts oxygen-related cell damage thought to contribute to Parkinson's”. The news site said that trials are underway to find a safe way to raise urate levels as a therapy.
The study involved 800 people with early Parkinson’s disease whose urate levels were measured before some took a treatment (alpha-tocopherol) for Parkinson's in a randomised controlled trial. An analysis of all the people together found that increased urate levels at the start of the study were linked with decreased risk of disease progression. The reason for this link is unclear.
In addition, the level of urate at the start did not seem to affect progression in people who received alpha-tocopherol treatment.
However, to determine whether or not urate treatment has a role in preventing the progression of Parkinson’s disease, far more research and investigation is required. Any possible harmful side effects from the treatment and who to treat are important questions to consider in future research.
Where did the story come from?
The research was carried out by Alberto Ascherio and colleagues from the Parkinson Study Group DATATOP Investigators. It was published in the Archives of Neurology. Funding was provided by grants from the National Institutes of Health, the US Department of Defense, the RJG Foundation, the Beeson Scholars/Hartford Collaborative Research program of the American Federation for Aging Research, the Parkinson Disease Foundation and the Parkinson Study Group.
What kind of scientific study was this?
This cohort study investigated how urate in the blood and cerebrospinal fluid surrounding the brain and spinal cord may affect the progression of Parkinson’s disease. Previous studies have suggested that there may be a link and that urate levels may be a predictor of the neurodegeneration (deterioration of nerve tissue) that leads to Parkinson’s disease.
This study involved 800 people participating in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) randomised controlled trial. This two-year Canadian trial enrolled people with early Parkinson’s disease (without severe symptoms and not currently using medications, with an average age of 62). It tested the theory that long-term treatment with monoamine oxidase type B inhibitor deprenyl (selegiline hydrochloride) and/or the antioxidant alpha-tocopherol would delay the onset of disability.
Researchers took a pre-treatment blood sample from 774 of the participants to check urate levels, and a sample of cerebrospinal fluid from 713 participants. The DATATOP researchers used clinical disability requiring levodopa therapy as the primary endpoint of the clinical trial. The results were adjusted for age, sex and the trial treatment received.
In this analysis, the association between urate levels and disease progression was analysed in people for whom measurements were available. The analysis also took into account the treatment group that the participant was in for the DATATOP trial.
What were the results of the study?
Increased serum urate concentrations were seen in everyone with a significant 36% decreased risk of progression to the primary endpoint, Parkinson’s disease disability that required treatment (hazard ratio for highest urate level compared to lowest: 0.64; 95% confidence interval 0.44 to 0.94).
Researchers also found that each unit increase in concentration (measured as a standard deviation, which is a way of showing how the data is distributed around the average) decreased the risk by 18%. When the researchers adjusted their calculations for alpha-tocopherol treatment, only those who did not receive the treatment showed a reduced risk of progression of disease (hazard ratio for a one-unit increase in urate: 0.75; 95% CI, 0.62 to 0.89).
Increased urate concentration in cerebrospinal fluid was also seen in people with a similar 35% decreased risk of Parkinson’s disease disability (hazard ratio for highest urate level vs lowest: 0.65; 95% CI 0.44 to 0.96), with 11% decreased risk with a one-unit increase in urate. As with serum urate concentration, when adjustments were made for alpha-tocopherol treatment, risk only decreased for people not treated with the drug.
What interpretations did the researchers draw from these results?
The researchers concluded that higher concentrations of urate in serum and cerebrospinal fluid at the start of the study were associated with slower rates of disease progression. They say that their results confirm the suspected association between urate concentration and Parkinson’s disease. They propose that the increasing urate concentration in the central nervous system may be a potential way of slowing progression.
What does the NHS Knowledge Service make of this study?
This relatively large study has strengths in that it obtained urate levels from 97% of its participants at the beginning of the study period. The results agree with those from previous studies and suggest that increasing urate concentration in people with Parkinson's may potentially decrease the rate of progression.
The reason for the link between urate and neuroprotection is unclear. The researchers suggest there may be an intermediate substance that is affecting the association or other determinants. The level of urate at the start did not seem to affect progression in people who received alpha-tocopherol treatment. The reason for this is not clear.
How the study population was recruited is not described in this publication. It is possible that it is a specific population, and if this was the case it would affect how the results can be applied to other groups. Also, these participants had early Parkinson’s disease, so this study cannot provide any information on how urate may have an effect when the disease is more established.
Whether or not urate treatment can help prevent the progression of Parkinson’s disease requires far more research and investigation. Potential harmful side effects of the treatment require investigation, along with research into which patient groups could be treated.