Researchers have discovered a substance in urine that may serve as a biomarkerfor predicting Parkinson’s disease (PD) risk and monitoring the progress of the disease. The results appear in the March 15 issue of Neurology and the June 15 online edition of Movement Disorders. The work was supported in part by the Parkinson’s Disease Foundation.
To date, there is no simple test, like a blood or urine test, for diagnosing Parkinson’s. Instead, doctors must interpret a person’s movement symptoms to diagnose PD. Because PD symptoms vary widely and overlap with those of other disorders, it is often misdiagnosed. That’s why scientists are searching for biomarkers — substances in the body, or detectable on brain scans — to definitively diagnose PD, predict PD risk or monitor disease progression.
In earlier studies, researchers led by Andrew B. West, Ph.D., at the University of Alabama, Birmingham, determined how to measure proteins in urine that are products of a gene that causes PD. About two to three percent of people with Parkinson’s have a mutation in the LRRK2 (leucine-rich repeat kinase 2) gene, although not everyone with the mutation develops PD.
For the study published in Neurology, researchers measured levels of a specific LRRK2 protein (phosphorylated LRRK2 protein) in the urine of 76 participants. They wanted to find out whether protein levels were tied to LRRK2 genetic mutations (in those with and without PD), and to PD without a LRRK2 mutation. In a second study, which appears in Movement Disorders, Dr. West’s research team measured LRRK2 protein levels in the urine of 79 men and women with PD and compared them to levels in 79 men and women who did not have PD.
- People with LRRK2 mutations, both those with and without PD, had elevated levels of the phosphorylated LRRK2 protein.
- Among those with the LRRK2 mutation, higher levels of the protein were associated with higher odds of having developed PD.
- LRRK2 protein levels were higher in men than in women.
- Among people with PD, higher levels of LRRK2 protein in the urine were associated with more cognitive difficulties.
- No significant association was found between high LRRK2 protein levels and movement difficulties.
What Does It Mean?
The discovery of genes linked to PD has changed our understanding of the causes of the disease. The next step in this research would be to manipulate activity of the proteins made by these genes. This might be helpful for people who carry genetic mutations, as well as others in the PD community.
In both new studies, researchers identified a specific form of LRRK2 protein which is significantly elevated in urine of carriers of the LRRK2 gene mutations. This finding could be extremely helpful one day, if certain experimental drugs (those which alter the activity of the protein) reach clinical trials. If that happens, it researchers would be able to measure the protein in urine, which would help them to confirm if drugs are indeed manipulating the activity of LRRK2.
The second study, published by the same group, indicates that the finding may be important even for those who do not carry LRRK2 mutation. People with PD, even without mutations, have a higher concentration of the phosphorylated LRRK2 than people without PD. Not only that, higher activity (as in mutation carriers) was associated with worse cognition. These findings argue that drugs blocking the gene may be useful for people with PD without the mutations.
If further studies do confirm the usefulness of measuring LRRK2 levels in urine, this biomarker could be combined with other tests to monitor, or potentially predict, the course of PD. Such a biomarker also might be used in clinical trials to predict who is most likely to respond to potential new therapies, and to monitor their effects.
Fraser KB, Moehle MS, Alcalay RN, West AB. (2016). Urinary LRRK2 Phosphorylation Predicts Parkinsonian Phenotypes in G2019S LRRK2 Carriers. Neurology 2016;86:994–999 DOI 10.1212/WNL.0000000000002436
Fraser KB, Rawlins AB, Clark RG, Alcalay RN, Standaert DG, Liu N, Parkinson’s Disease Biomarker Program Consortium, West AB. (2016). Ser(P)-1292 LRRK2 in Urinary Exosomes Is Elevated in Idiopathic Parkinson’s Disease. Movement Disorders, online 14 JUN 2016, DOI: 10.1002/mds.26686