Scientists have discovered that levels of a particular enzyme found in the urine of Parkinson’s disease sufferers can be reliably used to predict the severity of their symptoms. Though it is still not known how this enzyme causes the debilitating condition, the researchers behind the latest discovery believe that their work could lead to improvements in tracking the impact of experimental treatments for the disease.
Caused by a loss of neurons in a part of the brain called the substantia nigra, Parkinson’s is a progressive disease characterized by involuntary muscle shaking, yet also produces symptoms such as depression, insomnia and the loss of the sense of smell. Famously affecting the likes of Muhammad Ali and Michael J. Fox, the condition currently has no cure, though several types of therapy and experimental treatments have been reasonably successful at limiting the severity of the disease.
In March of this year, a study appeared in the journal Neurology, revealing that those who suffer from the condition have elevated levels of an enzyme called Ser(P)-1292 LRRK2 in their urine. This enzyme is produced by a genetic mutation that causes the normal LRRK2 enzyme to become autophosphorylated, meaning it adds too many phosphates to itself and other proteins.
Because LRRK2 is fairly large and is normally found in the central nervous system, the possibility of detecting it in urine had previously seemed remote. However, the study authors discovered that urine contains certain types of membrane-bound bubbles called exosomes, which enclose a variety of compounds released by cells throughout the body. Among the contents of these exosomes, they discovered LRRK2.
When analyzing the urine of their subjects, they discovered that those with Parkinson’s disease tended to have elevated levels of the phosphorylated form of the enzyme in their urine. On average the urine of sufferers contained five times more of this form of the enzyme than that of non-sufferers.
Image: Exosomes are a type of membrane-bound capsule, or vesicle, containing compounds released by cells throughout the body. Jamilia Marini/Shutterstock
Now, the same group of researchers has published a follow-up study in the journal Movement Disorders, looking at how levels of this mutated enzyme correlate with the severity of symptoms. Their findings not only confirm that urinary exosome levels of Ser(P)-1292 LRRK2 are higher in Parkinson’s disease patients than non-patients, but that the extent of a sufferer’s cognitive impairment and difficulty in accomplishing daily tasks is strongly linked to these levels.
This was evaluated using a number of standard cognition tests such as the Epworth Sleepiness Scale and the Montreal Cognitive Assessment test.
While the researchers still do not know how this mutated enzyme causes Parkinson’s, or indeed which body cells the urinary exosomes are excreted by, the fact that they have identified this biomarker could be a game-changer when testing out new treatments. For instance, by measuring how future medications affect levels of LRRK2 in the urine of those participating in clinical trials, researchers should be able to accurately gauge the effectiveness of these treatments.
As such, study co-author Andrew West explained in a statement that “the days of blindly testing new therapies for complex diseases like Parkinson’s without having active feedback both for ‘on-target’ drug effects and for effectiveness in patients are thankfully coming to an end,” adding that we could now be close to “stopping Parkinson’s disease in its tracks.”
Parkinson's disease is caused by a loss of neurons in certain key brain areas. Naeblys/Shutterstock