In this article, we will continue where we left off in the last newsletter in terms of research and neuroprotection in Parkinson’s Disease. This article may be read separately but is a continuation of the theme of neuroprotection research in Parkinson’s Disease.
Gout, the unwalkable disease, was first identified by Egyptians nearly 2,600 years BC, but the most famous reference is to the description by Hippocrates in the Fifth Century B.C. whose aphorism for Gout still hold true. Over the years, it has been referred to as the disease of kings because of its association with rich foods and alcohol consumption. The word gout comes from the Latin word ‘gutta’ and refers to the belief at that time that it results from a drop or flow into a joint of one of the four humours, causing pain and inflammation.
The disabling gouty arthritis of the British statesman William Pitt the elder, may have been a major factor in Britain’s loss of the American colonies as it resulted in his absence from parliament during acts when levies and taxes were passed on British colonies and later on the tea imports. The birth of America and the American Constitution have also been affected by gout as Benjamin Franklin, Thomas Jefferson and a French nobleman Vergennes were all severely affected by gout, and who can forget the famous gout attack of John Hancock that delayed the ratification of the Constitution by Massachusetts.
Crystals of uric acid in the joints causing gout were seen as far back as 1679 but were only described to be made of uric acid by 1776. It’s amazing that semi-quantitative method of measurement of uric acid in the serum or urine, the thread test, was the first-ever clinical chemical test to be designed in 1859.
But what is even more remarkable is that humans and primates (apes and monkeys) lost the ability of processing uric acid into something more soluble over the last 50 million years during the evolution as they gradually had changes in their genes and slowly lose the ability to process the uric acid into something more soluble, such as Allantoin. It’s still a curiosity why we lost the ability to process the uric acid into something that is less damaging and why we ended up with more uric acid in our system. One proposed hypothesis is that the ability to not process uric acid was somehow linked with increased ability to make fat from sugar. But what I want to tell you today is that uric acid could have saved us from having more Parkinson’s Disease, and let me tell you how.
Uric acid is the final product during metabolism of the building blocks of genes, or DNA. The uric acid, a simple molecule, has been linked with benefits on protecting against hypertension and potentially even being an antioxidant. What we have observed in large-population studies looking at the risk of Parkinson’s Disease is that the higher the uric acid levels in the blood the less likelihood that person belongs to a group with Parkinson’s Disease. So, prospective epidemiological studies have shown that the higher rate of uric acid in the blood is associated with a reduced risk of getting Parkinson’s Disease. The higher the level, the lower the risk. This has been confirmed through many large population studies including health professional follow-up study, Honolulu Heart Program and the Rotterdam study. It has also been shown that the diet that increases uric acid, the same linked with gout, is also linked with lower risk of Parkinson’s Disease.
Study of URate
This observation that among healthy individuals a high uric acid level predicts a reduced risk of Parkinson’s Disease have led to the hypothesis that among patients with the Parkinson’s Disease a high uric acid will predict a slower rate of progression of Parkinson’s Disease and will continue to provide the same protective benefits. To test this hypothesis, over the last 10 years a group of researchers have been looking at using high uric acid levels in various animal models of Parkinson’s Disease and then led to forming the concept of the current study, Sure PD3 (Study of URate Elevation in Parkinson’s Disease) to slow the progression of Parkinson’s Disease. In this study, we will be taking Parkinson’s Disease patients who have a low serum uric acid level, within the normal range, which are likely half to two-thirds of PD population and we will give them a supplement called Inosine to be converted into uric acid resulting in elevation of serum uric acid level. We be following the uric acid levels so that we bring them up to high normal range without overshooting the maximum level expected from a normal person, and then we will follow them over the two years while keeping the uric acid levels elevated to see if that results in delayed or slower progression of Parkinson’s Disease. This will be measured based on the rate of increase of their Unified Parkinson’s Disease Rating Scale (UPDRS). We will compare between two groups with only one getting the supplement. However, bringing up the uric acid level is not without risks. Even when the uric acid level is within normal range it can cause uric acid stones in the kidney and attack of gout. However, there is a risk that the uric acid level could overshoot because of the supplement without frequent testing, and thus the Inosine supplement dose is frequently adjusted in the study.
We have currently enrolled all of the required patients (270) that were needed for the study and we will now be following them for the next two years to look at the outcome or benefits that we are expecting because of a high uric acid level. Currently, it is not established that taking uric acid levels would actually be beneficial and is only a presumption at this time. While the risks are real and the side effects such as kidney stones have been observed in the ongoing trials. Therefore, it is not clinically recommended to check your uric acid levels or to take supplements to increase levels because of the associated risks, which are definitive; and an unknown benefit, which may not be there.