A protein linked to the presence and severity of Parkinson’s has been found in urine samples from patients — opening the possibility that it can be developed into a biomarker, greatly aiding disease diagnosis and research.
The finding, by researchers at the University of Alabama at Birmingham (UAB), led to two publications. In March, the study “Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019SLRRK2 carriers,” published in the journal Neurology, showed that urinary levels of the protein, called LRRK2, tagged with a phosphor molecule could be used to identify people at risk of developing Parkinson’s as well as those already ill. This study was done in people carrying a mutation in the LRRK2 gene, mutations found in only 2 percent to 3 percent of all Parkinson’s patients.
New research in patients without such mutations also found that LRRK2 concentrations in urine can mirror disease activity.
In the more recent study, “Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson’s disease,” published in the journal Movement Disorders, Andrew West and colleagues at UAB analyzed 158 urine samples from Parkinson’s patients without LRRK2 mutations and from healthy volunteers.
Surprisingly, they found that in about 20 percent of the patients, levels of phosphorylated LRRK2 were elevated at levels similar to those with a mutation — a finding not present in the healthy individuals. Levels were also higher among patients with greater cognitive problems.
Dr. West, the co-director of the Center for Neurodegeneration and Experimental Therapeutics, and the John A. and Ruth R. Jurenko Professor of Neurology at UAB, believes that the emergence of new biomarkers will revolutionize how doctors test for Parkinson’s disease in the future.
“I think the days of blindly testing new therapies for complex diseases like Parkinson’s … are thankfully coming to an end,” Dr. West said in a news release.
“Nobody thought we’d be able to measure the activity of this huge protein called LRRK2 (pronounced lark two) in biofluids since it is usually found inside neurons in the brain,” he said. “New biochemical markers like the one we’ve discovered, together with new neuroimaging approaches, are going to be the key to successfully stopping Parkinson’s disease in its tracks.”
Biomarkers are tools that make the work of physicians and researchers easier, presenting an objective way of measuring the presence of a disease, its progression or severity, and of measuring the effectiveness of a treatment. Ideally, such markers are found only in people with a particular disease, and not in healthy people or those with other conditions.
The lack of biomarkers in neurodegenerative disorders makes both research and care slow and suboptimal, since there is no way to set a diagnosis before extensive brain damage is already present. Likewise, when developing new drugs, their lack makes evaluation more complex.
But new technology and research approaches have advanced biomarker research in neurodegenerative conditions such as Parkinson’s. A recent discovery of small vesicles called exosomes in bodily fluids, holding proteins, RNA, and DNA, allowed Dr. West and his team to progress where others before him had failed.
Cells in the body continually release such exosomes, allowing the researchers to measure a substance in urine that is active in the brain.
In addition to neurons, LRRK2 is also found in immune cells, and the researchers are now trying to figure out where urinary LRRK2 comes from to better understand the disease processes mirrored by the elevated levels.