reposted from NP
Dr. Andrew West at the University of Alabama at Birmingham has been pioneering a new biomarker development approach aimed at detecting Parkinson’s. Dr. West focused first on studying the most common known genetic cause of Parkinson’s disease, the LRRK2 mutation. In patients with PD, it has been shown that the LRRK2 protein has more than expected phosphate groups clinging to its external structure, called phosphorylation. Dr. West’s approach is unique in that instead of trying to measure activity inside the body’s cells, he and his colleagues focused on measuring the exosome, which is located outside the cells. The exome contains proteins, RNA, and DNA that are all packaged into a container that is ejected from inside the cell.
You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease. You can read more from Dr. Okun in the What's Hot in PD? archives.
What's Hot in PD? Hot on the Trail for a Urine Biomarker for Parkinson’s Disease
What's Hot in PD? - August 2016
Previous What’s Hot blogs have addressed the promise and challenge of developing biomarkers for Parkinson’s disease (PD). Several groups of researchers have been working on blood and imaging biomarkers to provide more information on Parkinson’s: diagnosis, prediction, monitoring and methods to measure progression. In this month’s What’s Hot blog, we examine a new approach that utilizes a urine sample to detect the presence of Parkinson’s disease activity.
Dr. Andrew West at the University of Alabama at Birmingham has been pioneering a new biomarker development approach aimed at detecting Parkinson’s. Dr. West focused first on studying the most common known genetic cause of Parkinson’s disease, the LRRK2 mutation. In patients with PD, it has been shown that the LRRK2 protein has more than expected phosphate groups clinging to its external structure, called phosphorylation. Dr. West’s approach is unique in that instead of trying to measure activity inside the body’s cells, he and his colleagues focused on measuring the exosome, which is located outside the cells. The exome contains proteins, RNA, and DNA that are all packaged into a container that is ejected from inside the cell.
It turns out that Dr. West was able to measure the LRRK2 mutation and to pick up the presence of extra phosphate groups (phosphorylation) that cling to LRRK2. He proposed that measuring these phosphate groups on LRRK2 could be a urine biomarker for Parkinson’s disease.
Once Dr. West and his collaborators confirmed their observations by using urine from patients with LRRK2, they then tested urine from people with PD without the LRRK2 mutation. The researchers found that one in five people with Parkinson’s who do not have the LRRK2 mutation also had elevated phosphorylated LRRK2, but that non-disease controls did not show this effect. Dr. West and colleagues pondered whether this marker could be used to monitor the effects of PD medications and treatments in patients with baseline abnormalities on their urine screening test.
Though the urine biomarker for Parkinson’s will not apply to the majority of people with PD, it is an important first step. As we improve symptomatic and better targeted Parkinson’s therapies we will need better physiological markers of disease progression. Additionally, since the exosome is thought to play a major role in the immune system, these findings lend credibility to the potential role in inflammation in the development of Parkinson’s disease.
Selected References:
Kyle B. Fraser, Mark S. Moehle, Roy N. Alcalay, Andrew B. West. Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019SLRRK2carriers.Neurology, 2016; 86 (11): 994.
Kyle B. Fraser, Ashlee B. Rawlins, Rachel G. Clark, Roy N. Alcalay, David G. Standaert, Nianjun Liu, Andrew B. West. Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease. Movement Disorders, 2016.
You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease. You can read more from Dr. Okun in the What's Hot in PD? archives.
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