New research – Urate and Parkinson’s

New research this week lends further support to ongoing clinical trials focused on urate in Parkinson’s disease:

Title: Prospective study of plasma urate and risk of Parkinson disease in men and women.
Authors: Gao X, O’Reilly ÉJ, Schwarzschild MA, Ascherio A.
Journal: Neurology. 2016 Jan 13.
PMID: 26764029

The researchers in this study looked at 90,214 participants who are involved in three ongoing US-based longitudinal studies (the Nurses’ Health Study (NHS), the Cancer Prevention Study II Nutrition (CPS-IIN), and the Health Professionals Follow-up Study (HPFS)). They identified 388 people in these cohorts who had developed Parkinson’s disease (202 men and 186 women) since their respective longitudinal studies began, and they matched them to 1,267 randomly selected control subjects.

Blood samples that had been taken from the Parkinson’s and control subjects were analysed, and the level of urate was measured. Normal levels of urate range from 3.5-7.2 milligrams per deciliter (mg/dL). The researchers found that there was no difference between in spectrum of urate levels in the women (with or without Parkinson’s).

In men, however, things were very different. The men with the lowest levels of urate had less than 4.9 mg/dL, while those with the highest levels had 6.3-9.0 mg/dL. Among the men with Parkinson’s disease, 45 had the highest level of urate and 58 had the lowest – if no difference existed, this number should be 50:50, but instead there is more than 30% difference. Men with high levels of urate had a lower chance of developing Parkinson’s disease.

The researchers then combined their results with the results from three previous studies on the same topic and found a very similar result. This led the researchers to conclude that men, but not women, with higher urate concentrations had a lower future risk of developing Parkinson’s, suggesting that urate could be protective against Parkinson’s risk or could slow disease progression during the preclinical stage of disease.

So, what is urate?

During the breaking down of dietary proteins, the liver produces large amounts of a chemical called ‘ammonia’. Ammonia is toxic for the body, so the liver breaks it down further, and one of the products of that process is urate. If the body does not get rid of it, urate can build up and form crystals within the joints. High blood concentrations of urate can lead to gout and is also associated with other medical conditions, such as diabetes and the formation of kidney stones.

Paradoxically, urate is also an ‘antioxidant’ – a chemical that prevents tissue from being damaged by the negative effects of oxygen (yes, we need oxygen but not too much). Other antioxidants include vitamin C, and vitamin E. It is this antioxidant function of urate that researchers believe has a positive effect in Parkinson’s disease.

What are the clinical trials we mentioned?

In September 2015, a Phase III trial of Inosine was initiated. The study will involve 270 people with early-stage Parkinson’s. Inosine is a chemical precursor to urate and Phase III is the ‘acid test’ – a double blind test of treatment efficacy. A Michael J Fox Foundation-funded Phase II study showed that Inosine is safe and tolerable, and it also raised levels of urate in people with early-stage Parkinson’s disease. Now it is time to see if this raising of urate levels has a positive outcome. Enrollment for this trial is currently underway and -given the results of the study published this week – it will be interesting to see if there is a stronger effect in men in this phase III trial.

IMPORTANT EDITOR’S NOTE HERE: Inosine is commercially available as a dietary supplement, but we must stress that patients should act with caution. Inosine has not yet been proven as a therapy for Parkinson’s disease, and, as we indicated above, it can cause serious conditions such as gout and kidney stones. Please do not initiate usage of this chemical without first discussing it with your physician.